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Небесная энциклопедия

Космические корабли и станции, автоматические КА и методы их проектирования, бортовые комплексы управления, системы и средства жизнеобеспечения, особенности технологии производства ракетно-космических систем

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Мониторинг СМИ

Мониторинг СМИ и социальных сетей. Сканирование интернета, новостных сайтов, специализированных контентных площадок на базе мессенджеров. Гибкие настройки фильтров и первоначальных источников.

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Форма поиска

Поддерживает ввод нескольких поисковых фраз (по одной на строку). При поиске обеспечивает поддержку морфологии русского и английского языка
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Применить Всего найдено 2501. Отображено 100.
11-10-2012 дата публикации

Chimeric bacteriophage lysin with activity against staphylococci bacteria

Номер: US20120258088A1
Принадлежит: ROCKEFELLER UNIVERSITY

The present disclosure relates to chimeric bacteriophage lysins useful for the identification and/or reduction of staphylococcal populations. For example, a chimeric bacteriophage lysin was engineered and shown to effectively kill all strains of staphylococci tested including antibiotic resistant methicillin-resistant S. Aureus and VISA.

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29-11-2012 дата публикации

Packaging of Immunostimulatory Substances into Virus-Like Particles: Method of Preparation and Use

Номер: US20120301499A1
Принадлежит: Cytos Biotechnology AG

The invention relates to the finding that virus like particles (VLPs) can be loaded with immunostimulatory substances, in particular with DNA oligonucleotides containing non-methylated C and G (CpGs). Such CpG-VLPs are dramatically more immunogenic than their CpG-free counterparts and induce enhanced B and T cell responses. The immune response against antigens optionally coupled, fused or attached otherwise to the VLPs is similarly enhanced as the immune response against the VLP itself. In addition, the T cell responses against both the VLPs and antigens are especially directed to the Th1 type. Antigens attached to CpG-loaded VLPs may therefore be ideal vaccines for prophylactic or therapeutic vaccination against allergies, tumors and other self-molecules and chronic viral diseases.

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07-11-2013 дата публикации

Infectious cDNA of an approved vaccine strain of measles virus, use for immunogenic compositions

Номер: US20130296541A1
Принадлежит: Institut Pasteur de Lille

The invention relates to a cDNA molecule which encodes the nucleotide sequence of the full length antigenomic (+)RNA strand of a measles virus (MV) originating from an approved vaccine strain. It also contains the preparation of immunogenic compositions using said cDNA.

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19-12-2013 дата публикации

M13 Bacteriophage as a Chemoaddressable Nanoparticle for Biological and Medical Applications

Номер: US20130337435A1
Принадлежит: UNIVERSITY OF SOUTH CAROLINA

Reactive and modified M13 bacteriophages, and methods of making and using the same, are generally provided. The reactive M13 bacteriophage can include a alkyne functional group covalently attached to the M13 bacteriophage. The modified M13 bacteriophage can include a substituent covalently attached to the M13 bacteriophage via a 1,2,3-triazole linkage. Dual-modified M13 bacteriophages are also generally provided, and can include a cancer-targeting substituent covalently attached to the M13 bacteriophage and a fluorescent group covalently attached to the M13 bacteriophage. The modified M13 bacteriophages can not only be employed as a fluorescent probe for cancer imaging, but also can be used as biomaterials for cell alignment and scaffolding.

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26-12-2013 дата публикации

Continuous directed evolution

Номер: US20130345064A1
Принадлежит: Harvard College

The invention provides systems, methods, reagents, apparatuses, vectors, and host cells for the continuous evolution of nucleic acids. For example, a lagoon is provided in which a population of viral vectors comprising a gene of interest replicates in a stream of host cells, wherein the viral vectors lack a gene encoding a protein required for the generation of infectious viral particles, and wherein that gene is expressed in the host cells under the control of a conditional promoter, the activity of which depends on a function of the gene of interest to be evolved. Some aspects of this invention provide evolved products obtained from continuous evolution procedures described herein. Kits containing materials for continuous evolution are also provided.

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03-01-2019 дата публикации

NOVEL VIBRIO PARAHAEMOLYTICUS BACTERIOPHAGE VIB-PAP-2 AND USE THEREOF FOR INHIBITING PROLIFERATION OF VIBRIO PARAHAEMOLYTICUS

Номер: US20190000897A1
Принадлежит:

The present invention relates to a Podoviridae bacteriophage Vib-PAP-2 (Accession NO: KCTC 12910BP) that is isolated from the nature and can kill specifically cells, which has a genome represented by the nucleotide sequence of SEQ. ID. NO: 1, and a method for preventing and treating the infections of using the composition comprising said bacteriophage as an active ingredient. 1Vibrio parahaemolyticus. A Podoviridae bacteriophage Vib-PAP-2 (Accession NO: KCTC 12910BP) that is isolated from the nature and can kill cells specifically , which has the genome represented by the nucleotide sequence of SEQ. ID. NO: 1.2Vibrio parahaemolyticus. A composition for preventing and treating an infection of claim 1 , which comprises the bacteriophage Vib-PAP-2 of as an active ingredient.3Vibrio parahaemolyticus. The composition for preventing and treating an infection of according to claim 2 , wherein said composition is used to prepare an immersion agent or a feed additive.4Vibrio parahaemolyticus. A method for preventing or treating an infection of claim 2 , which comprises a step of administering to a subject the composition of comprising the bacteriophage Vib-PAP-2 as an active ingredient.5Vibrio parahaemolyticus. The method for preventing or treating an infection of according to claim 4 , wherein said composition is administered to a subject in the form of an immersion agent or a feed additive. The present invention relates to a bacteriophage isolated from the nature that infects and kills cells, and a method for preventing and treating the infections of using a composition comprising the bacteriophage as an active ingredient. More particularly, the present invention relates to a Podoviridae bacteriophage Vib-PAP-2 (Accession NO: KCTC 12910BP) that is isolated from the nature and can kill cells specifically, which has a genome represented by the nucleotide sequence of SEQ. ID. NO: 1, and a method for preventing the infections of and thereafter treating them using the ...

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03-01-2019 дата публикации

Phage therapy of pseudomonas infections

Номер: US20190002840A1
Принадлежит: Pherecydes Pharma SA

The present invention relates to bacteriophage therapy. More particularly, the present invention relates to novel bacteriophages having a high specificity against Pseudomonas aeruginosa strains, their manufacture, components thereof, compositions comprising the same and the uses thereof in phage therapy.

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12-01-2017 дата публикации

CONTINUOUS DIRECTED EVOLUTION

Номер: US20170009224A1
Принадлежит: President and Fellows of Harvard

The invention provides systems, methods, reagents, apparatuses, vectors, and host cells for the continuous evolution of nucleic acids. For example, a lagoon is provided in which a population of viral vectors comprising a gene of interest replicates in a stream of host cells, wherein the viral vectors lack a gene encoding a protein required for the generation of infectious viral particles, and wherein that gene is expressed in the host cells under the control of a conditional promoter, the activity of which depends on a function of the gene of interest to be evolved. Some aspects of this invention provide evolved products obtained from continuous evolution procedures described herein. Kits containing materials for continuous evolution are also provided. 150-. (canceled)51. An apparatus for continuous evolution of a gene of interest , the apparatus comprising(a) a lagoon comprisinga cell culture vessel comprising a population of M13 phages comprising a gene of interest to be evolved and lacking a functional pIII gene required for the generation of infectious phage particles, and a population of bacterial host cells, wherein(1) the M13 phages allow for expression of the gene of interest in the host cells,(2) the host cells are suitable host cells for M13 phage infection, replication, and packaging, wherein the M13 phage comprises all phage genes required for the generation of phage particles, except a functional pIII gene;(3) the host cells comprise an expression construct encoding the pIII protein, wherein expression of the pIII gene is dependent on a function of a gene product of the gene of interest;(4) the host cells comprise an expression construct encoding a dominant-negative pIII protein (pIII-neg), wherein the pIII-neg protein is driven by a promoter the activity of which depends on an undesired function of a gene product encoded by the gene of interest;an inflow connected to a turbidostat;an outflow;a controller controlling inflow and outflow rates; and(b) a ...

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14-01-2021 дата публикации

ONCOLYTIC T7 BACTERIOPHAGE HAVING CYTOKINE GENE AND DISPLAYING HOMING PEPTIDE ON CAPSID AND ITS USE FOR TREATING CANCER

Номер: US20210009963A1
Принадлежит: LYSENTECH

Provided is an oncolytic recombinant bacteriophage T7 expressing a cytokine in eukaryotic cells and displaying on its capsid a tumor specific homing peptide, thus inducing direct lysis of target tumor cells and immunological response to the phage leading to the effective anticancer effect. The phage naturally infecting bacteria, not human beings, provides a great advantage for gene manipulation and production for the development of anticancer agents. 1. An oncolytic recombinant bacteriophage T7 displaying on its capsid a tumor specific homing peptide and comprising a cytokine gene in the genome for expression in mammalian eukaryotic cell.2. The oncolytic recombinant bacteriophage T7 of claim 1 , wherein the cytokine is IL (Interleukin)-1α claim 1 , TNF (Tumor Necrosis Factor)-α claim 1 , GM-CSF (Granulocyte-Macrophage Colony-Stimulating Factor) claim 1 , IL-15 claim 1 , IL-2 claim 1 , IL-10 claim 1 , IL-12 claim 1 , TGF (Tumor Necrosis Factor)-β claim 1 , CSF-1 claim 1 , IL-8 claim 1 , VEGF (Vascular Endothelia Growth Factor) claim 1 , INF (Interferon)-α claim 1 , CCL (C—C motif chemokine) 2 claim 1 , CCL3 claim 1 , or CCL5.3. The oncolytic recombinant bacteriophage T7 of claim 1 , wherein the tumor is melanoma claim 1 , lung cancer claim 1 , prostate cancer claim 1 , glioblastoma claim 1 , pancreatic cancer claim 1 , leukemia claim 1 , or breast cancer.4. The oncolytic recombinant bacteriophage T7 of claim 1 , wherein the tumor specific homing peptide is represented by the amino acid sequence of CTVALPGGYVRVC set forth in SEQ ID NO: 1 for melanoma.5. The oncolytic recombinant bacteriophage T7 of claim 1 , wherein the tumor specific homing peptide is represented by the amino acid sequence of cyclic RGD-{-F}-{N-methyl-Val} for lung cancer and glioblastoma set forth in SEQ ID NO: 2.6. The oncolytic recombinant bacteriophage T7 of claim 1 , wherein the tumor specific homing peptide is the amino acid sequence of RTDLXXL set forth in SEQ ID NO: 3 for pancreatic cancer.7. ...

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03-02-2022 дата публикации

BACTERIOPHAGE FOR MODULATING INFLAMMATORY BOWEL DISEASE

Номер: US20220031776A1
Принадлежит:

Disclosed herein are bacteriophage compositions and therapeutic uses thereof. The disclosure also relates to bacteriophage that are capable of lysing bacterial strains, e.g., strains that are associated with inflammatory bowel disease, and thereby capable of modulating disease. 1) A pharmaceutical composition comprising at least two different lytic bacteriophage each selected from a different group , wherein the groups consist of:a) KP2W-P0101, KP2W-P0102, KP2W-P0103, KP2W-P0104, KP2W-P0105, KP2W-P0106, KP2W-P0107, KP2W-P0108, KP2W-P0109, and any other lytic bacteriophage that has at least 83% homology as determined by BLAST to any of the foregoing bacteriophage in a) and is capable of lytic infection of KP2 or a KP2 mutant,b) KP2M-P0201, KP2W-P0202, KP2M-P0203, KP2M-P0204, KP2M-P0205, KP2M-P0206, KP2M-P0207, KP2M-P0208, KP2M-P0209, KP2M-P0210, KP2M-P0211, KP2M-P0212, and any other lytic bacteriophage that has at least 85% homology as determined by BLAST to any of the foregoing bacteriophage in b) and is capable of lytic infection of KP2 or a KP2 mutant, and 'wherein the pharmaceutical composition is formulated for delivery to a mammalian intestine or formulated for delivery to a mammalian mouth.', 'c) KP2W-M0102, KP2W-M0103, KP2W-M0104, KP2M-M0105, KP2W-M0106, KP2W-M0107, KP2M-M0108, KP2M-M0109, KP2M-M0110, KP2M-M0111, KP2M-M0112, and any other lytic bacteriophage that has at least 86% homology as determined by BLAST to any of the foregoing bacteriophage in c) and is capable of lytic infection of KP2 or a KP2 mutant,'}2) The composition of claim 1 , comprising at least one bacteriophage selected from a)-c).3) The composition of claim 1 , comprising:a) KP2W-P0105 and KP2M-P0203,b) KP2M-P0203 and KP2W-M0104,c) KP2W-P0105 and KP2W-M0104,d) KP2W-P0102 and KP2M-P0209,e) KP2M-P0209 and KP2W-M0107,f) KP2W-P0102 and KP2W-M0107,g) KP2W-P0109 and KP2M-P0211,h) KP2M-P0211 and KP2M-M0112,i) KP2W-P0109 and KP2M-M0112,j) KP2W-P0105 and KP2M-P0203 and KP2W-M0104,k) KP2W-P0102 and ...

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03-02-2022 дата публикации

FUNCTIONALIZATION OF ENDOGENOUS BACTERIA

Номер: US20220033830A1
Принадлежит:

Various aspects and embodiments of the present disclosure are directed to methods and compositions for functionalizing endogenous bacteria in vivo. The methods include delivering to endogenous bacterial cells a recombinant bacteriophage or phagemid that is engineered to contain at least one genetic circuit. 121.-. (canceled)22. A recombinant bacteriophage that is engineered for in vivo delivery to endogenous bacterial cells to contain at least one genetic circuit , wherein the at least one genetic circuit does not express an antimicrobial protein.23. The recombinant bacteriophage of claim 22 , wherein the recombinant bacteriophage is a non-lytic recombinant bacteriophage.24. The recombinant bacteriophage of claim 23 , wherein the non-lytic recombinant bacteriophage is of a family selected from Myoviridae claim 23 , Siphoviridae claim 23 , Podoviridae claim 23 , Tectiviridae claim 23 , Corticoviridae claim 23 , Lipothrixviridae claim 23 , Plasmaviridae claim 23 , Rudiviridae claim 23 , Fuselloviridae claim 23 , Inoviridae claim 23 , Microviridae claim 23 , Leviviridae and Cystoviridae.25. The recombinant bacteriophage of claim 24 , wherein the non-lytic recombinant bacteriophage is an Inoviridae M13 or M13-like bacteriophage.26. The recombinant bacteriophage of claim 22 , wherein the at least one genetic circuit contains a nucleic acid with a promoter operably linked to a nucleotide sequence encoding a gene product.27. The recombinant bacteriophage of claim 26 , wherein the nucleic acid is a recombinant nucleic acid.28. The recombinant bacteriophage of claim 26 , wherein the nucleic acid is a synthetic nucleic acid.29. The recombinant bacteriophage of claim 26 , wherein the promoter is a constitutively active promoter.30. The recombinant bacteriophage of claim 26 , wherein the promoter is an inducible promoter.31. The recombinant bacteriophage of claim 26 , wherein the at least one genetic circuit is a recombinase-based genetic circuit.32. The recombinant ...

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18-01-2018 дата публикации

METHODS FOR MAKING ARRAYS FOR HIGH THROUGHPUT PROTEOMICS

Номер: US20180016299A1
Принадлежит:

Methods to obtain expression systems and proteins in a high-throughput protocol by utilizing mixtures of cells cultured from those transformed with a desired nucleotide sequence permit rapid production of protein for use in arrays to assess activity. In one embodiment, the proteins (or peptides) in the array are assessed for their immunological activity with regard to an infectious agent. 167to . (canceled)68. A method of making an array ,wherein the array comprises a plurality of different, individual and non-pure recombinant proteins and/or peptides of at least one pathogen, infectious agent or prokaryote having a known genome affixed on a plurality of distinct, individually addressable locations on a surface of a substrate, a plate or chip to produce an array of distinct, individually addressable locations,wherein the plurality of recombinant proteins and/or peptides comprises at least about 100 proteins and/or peptides and represents at least about 50% of the genome of the pathogen or infectious agent, or if the known genome is the genome of an infectious agent or the genome of the prokaryote, the plurality of different, individual and non-pure recombinant proteins and/or peptides comprises at least about 10% of the proteins and peptides expressed by the pathogen, infectious agent or prokaryote having a known genome,wherein the method of making the array comprises:(a) providing a plurality of linearized expression vectors;(b) providing a plurality of amplification primers comprising sequences capable of amplifying a desired number of open reading frame (ORF) coding sequences encoding the plurality of recombinant proteins and/or peptides expressed by the pathogen, infectious agent or prokaryote having a known genome,wherein each of the plurality of amplification primers contains both a sequence complementary to an end portion of one of the desired number of the ORF coding sequences and an adapter being homologous to a sequence provided on a linearized expression ...

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21-01-2021 дата публикации

POLYPEPTIDES COMPRISING A MODIFIED BACTERIOPHAGE G3P AMINO ACID SEQUENCE LACKING A GLYCOSYLATION SIGNAL

Номер: US20210015895A1
Принадлежит:

The invention relates to polypeptides that comprise a portion of filamentous bacteriophage gene 3 protein (g3p) sufficient to bind to and/or disaggregate amyloid, e.g., the N1-N2 portion of g3p and mutants and fragments thereof, wherein that g3p amino acid sequence has been modified through amino acid deletion, insertion or substitution to remove a putative glycosylation signal. The invention further relates to such polypeptides that are also modified through additional amino acid substitution to be substantially less immunogenic than the corresponding wild-type g3p amino acid sequence when used in vivo. The polypeptides of the invention retain their ability to bind and/or disaggregate amyloid. The invention further relates to the use of these g3p-modified polypeptides in the treatment and/or prevention of diseases associated with misfolding or aggregation of amyloid. 137-. (canceled)39. The polypeptide according to claim 38 , wherein the modification to remove the putative glycosylation signal at amino acids 39-41 of SEQ ID NO:1 or SEQ ID NO:2 is an amino acid substitution of N39.40. The polypeptide of claim 39 , wherein the modification to remove the putative glycosylation signal at amino acids 39-41 of SEQ ID NO:1 or SEQ ID NO:2 is an amino acid substitution selected from T41G claim 39 , T41W claim 39 , T41H claim 39 , T41V claim 39 , T41I claim 39 , T41L claim 39 , T41R claim 39 , T41K claim 39 , T41Y claim 39 , T41F claim 39 , T41D claim 39 , T41E claim 39 , T41Q claim 39 , T41N claim 39 , and T41A.4238. The polypeptide of claim 38 , wherein the starting amino acid sequence is modified by 2 to 9 amino acid substitutions selected from claim (b) claim 38 , wherein at least one substitution is present in epitope 1 claim 38 , comprising amino acids 48-56 of SEQ ID NO:1 or SEQ ID NO:2; and wherein at least one substitution is present in epitope 3 claim 38 , comprising amino acids 173-181 of SEQ ID NO:1 or SEQ ID NO:2.44. The polypeptide of claim 38 , consisting ...

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17-01-2019 дата публикации

PROTEOLIPOSOME AND PRODUCTION METHOD THEREOF

Номер: US20190017990A1
Автор: Jing Peng
Принадлежит: PURDUE RESEARCH FOUNDATION

The invention discloses a proteoliposome or a planar lipid bilayer membrane comprising a single protein manufactured using glycerol or polyethylene glycols (PEG) in the rehydration step. Products so prepared are useful for nanopore sensing technology, including ultrafast DNA sequencing and biomedical diagnostic applications. 1. A proteoliposome comprising a single protein , wherein said proteoliposome is manufactured according to the steps of:a) preparing a lipid solution in an organic solvent;b) preparing a protein solution;c) combining said lipid solution and said protein solution in a flask;d) removing said organic solvent from the combined solution from step c), under vacuum with constant mixing, to afford a residue;e) adding an aqueous buffer to the residue of step d), wherein said aqueous buffer is doped with glycerol or a polyethylene glycol (PEG);f) rehydrating the mixture of step e) by gentle agitation;g) extruding the rehydrated mixture of step f) through a polycarbonate membrane, wherein the polycarbonate membrane has a pore size ranging from about 50 nm to about 400 nm; andh) repeating step g) for about five to fifty times to afford a proteoliposome product.2. The proteoliposome of claim 1 , wherein said protein is a portal protein claim 1 , a channel protein claim 1 , or another membrane-bound protein.3. The proteoliposome of claim 1 , wherein said protein is selected from the group consisting of a mutant portal protein C-His GP10 from bacteriophage Phi29 claim 1 , a mutant portal protein GP20 (20amN50(Q325am)) from bacteriophage T4 claim 1 , hemolysin claim 1 , and MspA porin.4. The proteoliposome of claim 1 , wherein the concentration of said glycerol ranges from about 1% to about 99% (v/v).5. The proteoliposome of claim 1 , wherein the concentration of said glycerol ranges from about 10% to about 40% (v/v).6. The proteoliposome of claim 1 , wherein said polyethylene glycols (PEG) concentration ranges from about 0.1% to about 60% (v/v).7. The ...

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26-01-2017 дата публикации

TREATMENT OF TOPICAL AND SYSTEMIC BACTERIAL INFECTIONS

Номер: US20170020937A1
Принадлежит:

Bacteriophage covalently attached to a carrier particle with an average diameter of from 0.1 microns to 15 microns, are used in topical treatment of bacterial infection. Bacteriophage covalently attached to a carrier particle of average diameter 7 microns or less are used in systemic treatment of bacterial infection. A plurality of bacteriophages lytic against different bacterial strains gives wide antibacterial activity. A combination therapy comprises administration of antibiotic and bacteriophage covalently attached to a carrier particle. 150-. (canceled)51. A topical formulation , comprising a bacteriophage covalently attached to a carrier particle and a pharmaceutically acceptable carrier or excipient , wherein the topical formulation is formulated to treat a bacterial infection.52. The topical formulation of claim 51 , wherein the topical formation is a gel claim 51 , cream or lotion.53. The topical formulation of claim 52 , further comprising one or more agents selected from the group consisting of:a gel-forming agent,a cream-forming agent,a wax,an oil,a surfactant, anda binder.54. The topical formulation of claim 51 , wherein the carrier particle has an average diameter of up to 20 microns.55. The topical formulation of claim 51 , wherein the carrier particle has an average diameter of 0.1 microns to 15 microns.56. The topical formulation of claim 51 , wherein the carrier particle has an average diameter of 0.5 microns to 10 microns.57. The topical formulation of claim 52 , wherein:(a) the topical formulation is a cream or gel;(b) the bacteriophage is lytic for P. acnes; and(c) the carrier particle has an average diameter of up to 20 microns.58P. acnes.. The topical formulation of claim 57 , wherein the bacteriophage is lytic for at least 3 different strains of59. The topical formulation of claim 52 , wherein:(a) the topical formulation is a cream or gel;{'i': 'S. aureus;', '(b) the bacteriophage is lytic for and'}(c) the carrier particle has an average ...

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17-04-2014 дата публикации

Plasmids and methods for peptide display and affinity-selection on virus-like particles of rna bacteriophages

Номер: US20140106982A1
Принадлежит: Individual

The present invention relates to a system and method for controlling peptide display valency on virus-like particles (VLPs), especially including MS2 or PP7 VLPs. In this method, large amounts of wild-type and low quantities of single-chain dimer coat proteins may be produced from a single RNA. Valency is controlled in immunogen (vaccine) production by providing a system that allows the production of large amounts of wild-type and low quantities of single-chain dimer coating proteins from a single RNA, allowing facile adjustment of display valency levels on bacteriophage VLPs, especially MS2 or PP7 VLPs over a wide range, from few than one—on average—to as many as ninety per particle. This facilitates the production of immunogens and vaccines, including VLPs exhibiting low valency. Nucleic acid constructs useful in the expression of virus-like particles are disclosed, comprised of a coat polypeptide of bacteriophage such as MS2 or PP7 modified by insertion of a heterologous peptide, optionally comprising a carbohydrate mimotope, wherein the heterologous peptide is displayed on the virus-like particle and encapsidates bacteriphage mRNA.

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01-02-2018 дата публикации

Compositions and methods using capsids resistant to hydrolases

Номер: US20180030445A1
Принадлежит: Apse Inc

Novel processes and compositions are described which use viral capsid proteins resistant to hydrolases to prepare virus-like particles to enclose and subsequently isolate and purify target cargo molecules of interest including nucleic acids such as siRNAs and shRNAs, miRNAs, messenger RNAs, small peptides and bioactive molecules.

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30-01-2020 дата публикации

Phage therapy

Номер: US20200030392A1
Принадлежит: Pherecydes Pharma SA

The present invention relates to bacteriophage therapy. More particularly, the present invention relates to novel bacteriophages having a high specificity against Staphylococcus aureus strains, their manufacture, components thereof, compositions comprising the same and the uses thereof in phage therapy and as companion diagnostic.

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04-02-2021 дата публикации

Bacteriophages for food decontamination

Номер: US20210030031A1
Принадлежит: Aps Biocontrol Ltd

The disclosure provides phage-based methods, compositions and uses which may be applied to the prevention, management and/or control of microorganisms that cause damage, disease, spoilage and/or or loss of food, including vegetable, fruit and other fresh produce. The disclosure exploits bacteriophage (or “phage”) as a means to inactivate, kill or destroy microorganisms present on food and which are associated with, for example, disease, damage and spoilage (rotting).

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30-01-2020 дата публикации

MICROORGANISMS AND METHODS FOR PRODUCING BIOLOGICS AND INTRODUCING BIOLOGICS TO SITES

Номер: US20200030419A1
Принадлежит: WISCONSIN ALUMNI RESEARCH FOUNDATION

Microorganisms comprising a maltose-inducible promoter and methods of use in producing biologics and introducing biologics to sites in a maltose-dependent manner. The microorganisms include a maltose-inducible promoter operably connected to a coding sequence of a biologic. The biologic may be a polypeptide or a nucleic acid. Polypeptide biologics may include lytic proteins and/or secreted proteins. Nucleic acid biologics may include antisense RNA, other types of RNA, or other types of nucleic acids. The microorganisms can be used to produce the biologics and/or introduce the biologics to in vitro or in vivo sites in a maltose-dependent manner. The microorganisms can also be used in maltose-dependent gene silencing. 1. A microorganism harboring a recombinant gene , wherein the recombinant gene comprises a maltose-inducible promoter operably connected to a coding sequence of a first biologic , wherein the maltose-inducible promoter comprises a sequence at least about 90% identical to SEQ ID NO:1.2. The microorganism of claim 1 , wherein the first biologic comprises a lytic protein.3. The microorganism of claim 1 , wherein the first biologic comprises a lytic protein selected from the group consisting of a holin and a lysin.4. The microorganism of claim 1 , wherein the microorganism is genetically modified to produce a second biologic and wherein the first biologic effects release of the second biologic.5. The microorganism of claim 4 , wherein the second biologic is selected from the group consisting of a carbohydrate claim 4 , a polypeptide claim 4 , a nucleic acid claim 4 , a metabolite claim 4 , a virus claim 4 , and a combination thereof.6. The microorganism of claim 4 , wherein the second biologic is a polypeptide produced from a recombinant gene.7. The microorganism of claim 1 , wherein the first biologic comprises a polypeptide comprising a signal sequence.8. The microorganism of claim 1 , wherein the first biologic comprises an RNA.9. The microorganism of ...

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30-01-2020 дата публикации

PEPTIDE DISPLAYING BACTERIOPHAGE NANOPARTICLES AND RELATED COMPOSITIONS AND METHODS

Номер: US20200030433A1
Принадлежит:

Described herein is a fusion protein comprising a bacteriophage protein fused to a cancer antigen. Vaccines are also described, as well as methods of treatment and/or prevention of cancer and methods of immunizing an individual. 1. A fusion protein comprising gpD fused to a GP2 antigen and a linker linking the gpD and the GP2 antigen , wherein the linker comprises a GG repeat , a GS repeat , or a combination thereof.2. The fusion protein of claim 1 , wherein the gpD consists of or comprises an amino acid sequence at least about 90% claim 1 , 95% claim 1 , 97% claim 1 , 98% claim 1 , 99% or 100% identical to the amino acid sequence set forth in SEQ ID NO: 2.3. The fusion protein of claim 1 , wherein the GP2 antigen consists of or comprises the amino acid sequence set forth in SEQ ID NO: 6.4. The fusion protein of claim 1 , wherein the GP2 antigen is immunogenic.5. The fusion protein of claim 1 , wherein the linker consists of or comprises an amino acid sequence encoded by a nucleic acid sequence having at least 90% identity to the sequence set forth in SEQ ID NO 3.6. The fusion protein of claim 1 , wherein the linker comprises an amino acid sequence at least about 90% claim 1 , 95% claim 1 , 97% claim 1 , 98% claim 1 , 99% or 100% identical to the amino acid sequence set forth in SEQ ID NO: 4.7. The fusion protein of claim 1 , wherein the fusion protein consists of or comprises an amino acid sequence encoded by a nucleic acid sequence having at least about 90% identity to the sequence set forth in SEQ ID NO 11.8. The fusion protein of claim 1 , wherein the fusion protein consists of or comprises the amino acid sequence set forth in SEQ ID NO: 12.9. A method for treating cancer in a subject in need thereof claim 1 , comprising administering to the subject a fusion protein comprising gpD fused to a GP2 antigen and a linker linking the gpD and the GP2 antigen claim 1 , wherein the linker comprises a GG repeat claim 1 , a GS repeat claim 1 , or a combination thereof.10. ...

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30-01-2020 дата публикации

Bacteriophage-based electrochemical bacterial sensors, systems, and methods

Номер: US20200033340A1

The present disclosure includes methods and systems of detecting bacteria in a sample using phage-functionalized sensors, methods of enriching a sample with phage-functionalized magnetic particles, phage-functionalized magnetic particles and methods of making phage-functionalized magnetic particles.

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09-02-2017 дата публикации

NOVEL BACTERIOPHAGE AND COMPOSITION COMPRISING SAME

Номер: US20170037380A1
Принадлежит: CJ CHEILJEDANG CORPORATION

The present invention relates to a novel bacteriophage ΦCJ28 (KCCM11466P) and a composition containing the same as an active ingredient. Further, the present invention relates to a method for preventing and/or treating infective diseases caused by enterotoxic (ETEC) of animals excluding humans by using the composition. 1Escherichia coli.. A bacteriophage ΦCJ28 (KCCM11466P) having a specific ability to kill enterotoxigenic2Escherichia coli. A composition for preventing and/or treating infectious diseases caused by enterotoxigenic comprising the bacteriophage ΦCJ28 (KCCM11466P) according to as an active ingredient.3Escherichia coli. The composition for preventing and/or treating infectious diseases caused by enterotoxigenic according to claim 2 , wherein the infectious disease is colibacillosis.4. An antibiotic comprising the bacteriophage ΦCJ28 (KCCM11466P) according to as an active ingredient.5. An additive for feeds comprising the bacteriophage ΦCJ28 (KCCM11466P) according to as an active ingredient.6. Feeds comprising the additive for feeds according to .7. An additive for drinking water comprising the bacteriophage ΦCJ28 (KCCM11466P) according to as an active ingredient.8. Drinking water comprising the additive for drinking water according to .9. A disinfectant comprising the bacteriophage ΦCJ28 (KCCM11466P) according to as an active ingredient.10. A detergent comprising the bacteriophage ΦCJ28 (KCCM11466P) according to as an active ingredient.11Escherichia coli. A method for preventing or treating infectious diseases caused by enterotoxigenic claim 1 , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'administering the bacteriophage ΦCJ28 (KCCM11466P) according to to a non-human animal.'}12Escherichia coli. The method for preventing or treating infectious diseases caused by enterotoxigenic according to claim 11 , wherein the infectious disease is colibacillosis.13Escherichia coli. A method for preventing or treating infectious diseases caused by ...

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24-02-2022 дата публикации

A METHOD FOR DEPLETION OR REMOVAL OF ENDOTOXIN FROM AN ENDOTOXIN-CONTAINING SOURCE OR POTENTIALLY ENDOTOXIN-CONTAINING SOURCE

Номер: US20220056421A1
Принадлежит:

A method for depletion or removal of endotoxins from a known or suspected endotoxin-containing source by virtue of a solid phase extraction material in an essentially aqueous system comprising the steps of—providing a known or suspected endotoxin-containing source, —contacting the known or suspected endotoxin-containing source with a positively charged solid phase material having a surface on which ferric iron is immobilised, wherein the solid phase extraction material has immobilised the ferric iron by (2-aminoethyl)amine (TREN) ligand—incubating the known or suspected endotoxin-containing source for a period of time sufficient to bind endotoxin to the porous solid phase material, —separating the solid phase material from the essentially aqueous system, —optionally isolating the essentially aqueous system freed or depleted from endotoxin. 1. A method for depletion or removal of endotoxins from a known or suspected endotoxin-containing source by virtue of a solid phase extraction material in an essentially aqueous system comprising the steps ofproviding a known or suspected endotoxin-containing source;contacting the known or suspected endotoxin-containing source with a positively charged solid phase material having a surface on which ferric iron is immobilised, wherein the solid phase extraction material has immobilised the ferric iron by (2-aminoethyl)amine (TREN) ligand;incubating the known or suspected endotoxin-containing source for a period of time sufficient to bind endotoxin to the porous solid phase material; andseparating the solid phase material from the essentially aqueous system.2. The method of claim 1 , wherein the solid-phase extraction is a method selected from the group consisting of chromatography claim 1 , filtration claim 1 , co-precipitation and combinations thereof.3. The method of claim 1 , wherein the solid phase material comprises a chromatographic material which depletes or removes the endotoxin by ferric iron chelation from the known or ...

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12-02-2015 дата публикации

TARGET-SPECIFIC PROBE COMPRISING T7 BACTERIOPHAGE AND DETECTING FOR BIOMARKER USING THE SAME

Номер: US20150044665A1

The present invention relates to a target-specific probe containing T7 bacteriophage with a targeting antibody, and a detection method or a detection kit for a biomarker using the target-specific probe. The biomarker can be detected by using the genetically-modified T7 bacteriophage expressing various heterogeneous proteins and peptides on its surface and antibody-antigen specific reaction which can make the probe targeted to a biomarker or bacteria; and a detectable labeling agent, for example a quantum dot. 1. A target-specific probe including a binding peptide bound to a head part of T7 bacteriophage , a targeting antibody connected to the binding peptide , and a detectable labeling agent bound to a tail part of T7 bacteriophage.2. The target-specific probe according to claim 1 , wherein the binding peptide is protein G claim 1 , protein A claim 1 , protein A/G claim 1 , Fc receptor claim 1 , protein Z or a biotinylation tag.3. The target-specific probe according to claim 1 , wherein the targeting antibody is connected to the binding peptide through Fc part of the targeting antibody.4. The target-specific probe according to claim 1 , wherein the binding peptide is provided by a fusion peptide where the binding peptide is bound to a C-terminus of the head part of T7 bacteriophage.5. The target-specific probe according to claim 1 , wherein the targeting antibody is bound to the binding peptide via HIS Tag claim 1 , CYS Tag claim 1 , GST Tag or biotinylation binding tag.6. The target-specific probe according to claim 1 , wherein the labeling agent is bound to the tail part of T7 bacteriophage via HIS Tag claim 1 , CYS Tag claim 1 , GST Tag or biotinylation binding tag.7. The target-specific probe according to claim 6 , wherein the tag is inserted into the internal site in the tail part of T7 bacteriophage or connected to an end of the tail part of T7 bacteriophage.8. The target-specific probe according to claim 1 , wherein the T7 bacteriophage is an modified T7 ...

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06-02-2020 дата публикации

NOVEL ANTI-CRISPR GENES AND PROTEINS AND METHODS OF USE

Номер: US20200040328A1
Принадлежит:

The invention relates to anti-CRISPR genes and anti-CRISPR proteins, and their uses in various biotechnology applications 1. A method to favor the screening of a bacterial mechanism providing resistance against a virulent phage other than a given class 2 type II CRISPR-Cas mediated resistance , comprising:1) providing a bacterial strain, the genome of which contains a given class 2 type II CRISPR-Cas system, which is known to be active against target nucleic acids;2) expressing in said bacterial strain a gene encoding a protein which interferes with a function of said given class 2 type II CRISPR-Cas system;3) exposing said bacterial strain of step 2) to a virulent phage; and4) selecting bacteriophage-insensitive mutants (BIMs),wherein the resistance in said selected BIMs is provided by a bacterial mechanism other than the given class 2 type II CRISPR-Cas-mediated resistance.2. The method of claim 1 , wherein said bacterial mechanism providing phage resistance to said BIMs selected in step 4) is a mechanism mediated by another CRISPR-Cas system.3. A method to enrich a bacterial population in bacteriophage-insensitive mutants (BIMs) other than BIMs due to a given CRISPR-Cas system claim 1 , comprising:1) providing a bacterial strain, the genome of which contains a given class 2 type II CRISPR-Cas system, which is known to be active against target nucleic acids2) expressing in said bacterial strain a gene encoding a protein which interferes with a function of said given class 2 type II CRISPR-Cas system;3) exposing said bacterial strain of step 2) to a virulent phage4) selecting BIMs,wherein the selected BIMs have acquired resistance to said phage by a mechanism other than the given class 2 type II CRISPR-Cas system.4. The method according to any of to claim 1 , wherein said protein which interferes with a function of a given class 2 type II CRISPR-Cas system is a protein which interferes with the interference function of a class 2 type II CRISPR-Cas system and ...

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19-02-2015 дата публикации

BACTERIOPHAGES EXPRESSING ANTIMICROBIAL PEPTIDES AND USES THEREOF

Номер: US20150050717A1
Принадлежит:

The present invention is generally related to engineered bacteriophages expressing antimicrobial peptides or lytic enzymes or fragments thereof for targeting a broad spectrum of bacterial hosts, and for the long-term suppression of bacterial phage resistance for reducing bacterial infections. In some embodiments, bacteriophages express antimicrobial peptides or antimicrobial polypeptides (e.g. phage lytic enzymes) which are secreted from the host bacteria, or alternatively released upon lysis of the bacterial host cell. Aspects of the present invention also relate to the use of the engineered bacteriophages for the reduction of bacterial infections, both in a subject or for bioremediation purposes, in clinical settings and wound healing. 1. A method to reduce a population of bacterial cells comprising administering to a surface infected with the bacterial cells at least one bacteriophage comprising a nucleic acid operatively linked to a promoter , wherein the nucleic acid encodes at least one antimicrobial polypeptide.2. The method of claim 1 , wherein the antimicrobial polypeptide is an antimicrobial peptide or a naturally occurring bacterial peptide.3. The method of claim 1 , wherein the antimicrobial peptide is selected from the group comprising: Indolicidin (SEQ ID NO: 6) claim 1 , Cecropin P1 (SEQ ID NO: 11) claim 1 , Dermaseptin (SEQ ID NO: 14) claim 1 , Ponericin W1 (SEQ ID NO: 44) claim 1 , Ponericin W3 (SEQ ID NO: 40) claim 1 , Ponericin W4 (SEQ ID NO: 18) claim 1 , Ponericin W5 (SEQ ID NO: 42) claim 1 , Ponericin W6 (SEQ ID NO: 22) or variants thereof.4. The method of claim 1 , wherein the antimicrobial polypeptide is a lytic enzyme.5. The method of claim 1 , wherein the lytic enzyme is LysK or a functional fragment thereof.6. The method of claim 5 , wherein the functional fragment of LysK is CHAP165 (SEQ ID NO: 71) or a variant thereof.7. The method of claim 1 , wherein the bacteria is present in a subject.8. The method of claim 7 , wherein the subject is ...

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22-02-2018 дата публикации

IMMUNOTHERAPY COMPOSITIONS AND METHODS FOR TREATMENT OF TAUOPATHY AND TRANSGENIC MOUSE

Номер: US20180050097A1
Принадлежит:

This disclosure describes, in one aspect, immunogens effective for treating and/or diagnosing tauopathy, and immunotherapeutic compositions and methods involving those immunogens. Generally, the immunogen includes an antigen presentation component and a microtubule-associated tau protein (MAPT) component linked to at least a portion of the antigen presentation component. This disclosure describes, in another aspect, a transgenic mouse. Generally, the transgenic mouse possesses brain cells that have a polynucleotide that encodes human microtubule-associated protein tau (MAPT). The polynucleotide further exhibits a deletion of at least a portion of endogenous mouse MAPT. The transgenic mouse also includes a forebrain neuron-specific deletion of a polynucleotide that encodes Myeloid Differentiation Primary Response Gene 88 (MyD88). In a further aspect, this disclosure describes a method of producing the transgenic mouse. 1. An immunogen comprising:an antigen presentation component; anda microtubule-associated tau protein (MAPT) component linked to at least a portion of the antigen presentation component.2. The immunogen of wherein the MAPT component comprises at least one amino acid residue modified to comprise a POHgroup.3. The immunogen of wherein the MAPT component comprises the amino acid sequence of any one of SEQ ID NO:1 claim 2 , SEQ ID NO:2 claim 2 , SEQ ID NO:3 claim 2 , SEQ ID NO:4 claim 2 , SEQ ID NO:5 claim 2 , SEQ ID NO:6 claim 2 , SEQ ID NO:7 claim 2 , SEQ ID NO:8 claim 2 , SEQ ID NO:9 claim 2 , SEQ ID NO:10 claim 2 , SEQ ID NO:11 claim 2 , SEQ ID NO:12 claim 2 , SEQ ID NO:13 claim 2 , SEQ ID NO:14 claim 2 , SEQ ID NO:15 claim 2 , SEQ ID NO:16 claim 2 , SEQ ID NO:17 claim 2 , SEQ ID NO:18 claim 2 , SEQ ID NO:19 claim 2 , SEQ ID NO:20 claim 2 , SEQ ID NO:21 claim 2 , SEQ ID NO:22 claim 2 , SEQ ID NO:23 claim 2 , SEQ ID NO:24 claim 2 , SEQ ID NO:25 claim 2 , SEQ ID NO:26 claim 2 , SEQ ID NO:27 claim 2 , SEQ ID NO:28 claim 2 , SEQ ID NO:29 claim 2 , SEQ ID ...

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25-02-2021 дата публикации

PROKARYOTIC-EUKARYOTIC HYBRID VIRAL VECTOR FOR DELIVERY OF LARGE CARGOS OF GENES AND PROTEINS INTO HUMAN CELLS

Номер: US20210054410A1
Принадлежит:

Described is hybrid viral vector comprising: a first virus such as bacteriophage T4; one or more second virus such as adeno-associated virus (AAV) attached to the first virus through cross-bridges, such as avidin-biotin cross-bridges; one or more DNA molecules packaged in the first virus; one or more nucleic acid molecules packaged in the second virus; and one or more proteins displayed on the surface of the first virus. Also described are methods of making and using such a hybrid viral vector. 1. A product comprising:a first viral vector;a second viral vector; anda cross-bridge connecting the eukaryotic viral vector to the prokaryotic viral vector.2BacillusEscherichia coli. The product of claim 1 , wherein the first viral vector is selected from the group consisting of Lambda phage claim 1 , phage Phi29 claim 1 , phages T2 claim 1 , T3 claim 1 , and T7 claim 1 , Enterobacteriaphage P22 claim 1 , phage SPP1 claim 1 , Herpes viruses and adenoviruses.3. The product of claim 1 , wherein the second viral vector is selected from the group consisting of adenoviruses claim 1 , adeno-associated viruses (AAV) claim 1 , retroviruses claim 1 , lentiviruses and combinations thereof.4. The product of claim 1 , wherein the cross-bridge is selected from the group consisting of SBA claim 1 , HBBA and combinations thereof.5. The product of claim 1 , further comprising one or more DNA molecules packaged in the first viral vector.6. The product of claim 5 , wherein the DNA is double stranded.7. The product of claim 1 , further comprising one or more nucleic acid molecules packaged in the second viral vector.8. The product of claim 7 , wherein the nucleic acid is selected from the group consisting of single stranded DNA claim 7 , double stranded DNA and RNA.9. The product of claim 1 , further comprising one or more double stranded DNA molecules packaged in the first viral vector and one or more nucleic acid molecules packaged in the second viral vector.10. The product of claim 1 , ...

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10-03-2022 дата публикации

ACINETOBACTER BAUMANNII BACTERIOPHAGE MIKAB48 OR LYTIC PROTEIN DERIVED FROM THE BACTERIOPHAGE

Номер: US20220073567A1
Автор: COTAK Medine

A novel bacteriophage and lytic protein derived from the bacteriophage are disclosed. The bacteriophage and lytic protein derived from the bacteriophage both have strong in vitro antibacterial effects on pan-drug resistant clinical strains providing experimental basis for developing a preparation for preventing and treating infections caused by containing the bacteriophage or lytic protein thereof. 1. (canceled)2Acinetobacter baumannii. A gene coding a lytic protein , wherein the lytic protein is derived from an isolated phage comprising a genome set forth in SEQ ID NO: 1 , and the gene encoding the lytic protein is set forth in SEQ ID NO: 2.3Acinetobacter baumannii. A lytic protein , wherein the lytic protein is derived from an isolated phage comprising a genome set forth in SEQ ID NO: 1 , and an amino acid sequence of the lytic protein is set forth in SEQ ID NO: 3.4Acinetobacter baumannii. A pharmaceutical composition for prevention and treatment of diseases caused by claim 2 , comprising a vector carrying the gene according to .5. The pharmaceutical composition according to claim 4 , comprising a vector carrying a gene of a lytic protein having at least 80% similarity to SEQ ID NO: 2.6Acinetobacter baumannii. A pharmaceutical composition for prevention and treatment of diseases caused by claim 3 , comprising the lytic protein according to .7. The pharmaceutical composition according to claim 6 , comprising an antibacterial peptide comprising of an amino acid sequence having at least 82% similarity to SEQ ID NO: 3.8Acinetobacter baumanniiAcinetobacter baumannii. A method of preventing and treating diseases caused by claim 2 , comprising the step of using the isolated phage of alone or in combination with other antibiotics or antimicrobial peptides.9. The pharmaceutical composition according to claim 4 , further comprising an antibiotic claim 4 , a disinfectant claim 4 , a medical cleaner claim 4 , an antibacterial agent claim 4 , an antibacterial cream claim 4 , a ...

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21-02-2019 дата публикации

Novel cell membrane-permeating peptide

Номер: US20190054148A1
Автор: Shingo Ito, Sumio Ohtsuki
Принадлежит: Kumamoto University NUC

The present invention addresses to provide a novel membrane permeability-improving agent which can be applied to high molecular drugs. More specifically, the present invention addresses to provide: a drug carrier which can improve the absorption efficiency of a high molecular drug in the small intestine; and a membrane permeation-improving agent containing the carrier. According to the present invention, a cell membrane-permeating peptide can be provided, which comprises an amino acid sequence selected from the group consisting of the following amino acid sequences: DNPGN (SEQ ID NO: 1); SRPAF (SEQ ID NO: 2); NDPRN (SEQ ID NO: 3); and MSVAN (SEQ ID NO: 4). According to the present invention, a cell membrane-permeable composition can also be provided, which comprises the peptide and a biologically active substance.

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10-03-2022 дата публикации

EVOLUTION OF SITE-SPECIFIC RECOMBINASES

Номер: US20220073887A1

Some aspects of the present disclosure provide methods for evolving recombinases to recognize target sequences that differ from the canonical recognition sequences. Some aspects of this disclosure provide evolved recombinases, e.g., recombinases that bind and recombine naturally-occurring target sequences, such as, e.g., target sequences within the human Rosa26 locus. Methods for using such recombinases for genetically engineering nucleic acid molecules in vitro and in vivo are also provided. Some aspects of this disclosure also provide libraries and screening methods for assessing the target site preferences of recombinases, as well as methods for selecting recombinases that bind and recombine a non-canonical target sequence with high specificity. 165-. (canceled)67. The method of claim 66 , wherein:(i) the left half-site of the recombinase target sequence is not a palindrome of the right half-site;(ii) the recombinase target sequence is a naturally occurring sequence;(iii) the recombinase target sequence is in the genome of a mammal;(iv) the recombinase target sequence is in the genome of a human; or(v) the recombinase target site occurs only once in the genome of a mammal.6872-. (canceled)73. The method of claim 66 , wherein the recombinase target sequence is located in a safe harbor genomic locus or wherein the recombinase target sequence is located in a genomic locus associated with a disease or disorder.7478-. (canceled)79. The method of claim 66 , wherein the method comprises administering a composition comprising the recombinase and the second nucleic acid molecule to the subject in an amount sufficient for the recombinase to bind and recombine the first recombinase target sequence claim 66 , resulting in an integration of all or part of the second nucleic acid into the genome of a cell of the subject.80. A method for identifying a target site of a recombinase claim 66 , the method comprising(a) providing a recombinase that binds and recombines a double- ...

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10-03-2022 дата публикации

ARTIFICIAL RIBOSOMES FOR FULLY PROGRAMMABLE SYNTHESIS OF NONRIBOSOMAL PEPTIDES

Номер: US20220073897A1
Автор: Green Alexander A.
Принадлежит:

Provided herein, in some embodiments, are artificial ribosomes that synthesize nonribosomal peptides, polyketides, and fatty acids with full control over peptide sequence. Also provided herein are methods for programmed synthesis of nonribosomal peptides, polyketides, and fatty acids. In particular, provided herein are methods for scalable synthesis of a wide range of antibacterial, antifungal, antiviral, and anticancer compounds. 114.-. (canceled)16. The molecular assembly line of claim 15 , wherein the synthetic RNA scaffold is a tRNA analog.17. The molecular assembly line of claim 15 , wherein at least one fusion protein comprises a RNA-binding peptide selected from Lambda(G1N2R4) claim 15 , P22N claim 15 , RevN7D claim 15 , HTLV-1-Rex claim 15 , and BIV-Tat.18. The molecular assembly line of claim 17 , wherein at least one RNA binding peptide binds to an aptamer sequence within a tRNA analog.19. A synthetic nucleic acid sequence encoding the molecular assembly line of .20. A biological cell comprising the synthetic nucleic acid sequence of .21. A method for assembling the molecular assembly line of claim 15 , the method comprising:(a) providing the molecular assembly line to a cell-free expression system; and(b) incubating the cell-free system containing the molecular assembly line under conditions wherein the at least two fusion proteins are able to bind to the synthetic RNA scaffold.22. The method of claim 21 , wherein the synthetic RNA scaffold comprises tRNA analogs.23. The method of claim 21 , wherein at least one RNA-binding peptide comprises an RNA-binding domain from a protein selected from Lambda N claim 21 , P22N claim 21 , RevN7D claim 21 , HTLV-1-Rex claim 21 , and BIV-Tat.24. The method of claim 23 , wherein at least one RNA-binding peptide binds to an aptamer sequence within a tRNA analog. This application claims priority to U.S. Provisional Application No. 62/616,061, filed Jan. 11, 2018, which is incorporated herein by reference as it set forth ...

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04-03-2021 дата публикации

PHAGE THERAPY OF E COLI INFECTIONS

Номер: US20210060100A1
Принадлежит:

The present invention relates to bacteriophage therapy. More particularly, the present invention relates to novel bacteriophages having a high specificity against strains, their manufacture, components thereof, compositions comprising the same and the uses thereof in phage therapy. 1Escherichia coliE. coli. An antibacterial composition comprising at least one bacteriophage having lytic activity to an () strain , said at least one bacteriophage being selected from the bacteriophages having a genome comprising a nucleotide sequence selected from any one of SEQ ID NOs: 1 to 15 or a sequence having at least 90% identity thereto.2. The composition of claim 1 , comprising at least one of the bacteriophages BP539 claim 1 , BP700 claim 1 , BP753 claim 1 , BP814 claim 1 , BP953 claim 1 , BP954 claim 1 , BP970 claim 1 , BP1002 claim 1 , BP1151 claim 1 , BP1155 claim 1 , BP1168 claim 1 , BP1176 claim 1 , BP1197 claim 1 , BP1226 and BP1229 comprising the nucleotide sequence of SEQ ID NOs: 1 to 15 claim 1 , respectively.3E. coli. The composition of claim 1 , which is lytic against antibiotic-resistant strains.4. The composition of claim 1 , which is lytic against more that 90% of all bacterial strains of EcoR collection.5. The composition of claim 1 , which further comprises a pharmaceutically acceptable excipient or carrier.6. The composition of claim 1 , which is a liquid claim 1 , semi-liquid claim 1 , solid or lyophilized formulation.7. The composition of claim 1 , which comprises between 10and 10PFU of bacteriophage.8E. coliE. coliE. coli. The composition of claim 1 , wherein the bacteriophage has lytic activity to a pathogenic strain claim 1 , and wherein the bacteriophage (i) is specific for (ii) is active against antibiotic-resistant strains claim 1 , and (iii) has a productive lytic effect (“PLE”) below 15.9. A method of treatment of an infection in a mammal claim 1 , comprising administering to the mammal a composition of .10. A method for improving the condition of a ...

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04-03-2021 дата публикации

SEQUENCE SPECIFIC ANTIMICROBIALS

Номер: US20210060140A1
Принадлежит:

Provided are compositions and methods for selectively reducing the amount of antibiotic resistant and/or virulent bacteria in a mixed bacteria population, or for reducing any other type of unwanted bacteria in a mixed bacteria population. The compositions and methods involve targeting bacteria that are differentiated from other members of the population by at least one unique clustered regularly interspaced short palindromic repeats (CRISPR) targeted DNA sequence. The compositions and methods can be readily adapted to target any bacteria or any bacteria plasmid, or both. 114.-. (canceled)15. A method for killing targeted bacteria in a mixed bacterial population comprising:providing a pharmaceutical composition comprising a pharmaceutically acceptable carrier and packaged, recombinant phagemids that are packaged in phage capsids,wherein the packaged phagemids comprise a clustered regularly interspaced short palindromic repeats (CRISPR) system,wherein the CRISPR system comprises DNA encoding: i) a type II CRISPR-associated enzyme; and ii) a targeting RNA that targets at least one bacterial chromosome at a target site; andcontacting the bacterial population with the pharmaceutical composition,wherein the contacting with the pharmaceutical composition introduces at least some of the phagemids into at least some of the bacteria in the bacterial population,wherein subsequent to the introduction of the phagemids, the bacteria into which the phagemid is introduced expresses the targeting RNA and the type II CRISPR-associated enzyme,wherein the expressed type II CRISPR-associated enzyme cleaves the bacterial chromosome at the target site of the targeting RNA, andwherein the cleavage of the bacterial chromosome at the target site kills the bacteria;{'i': 'Staphylococcus aureus.', 'wherein the mixed bacterial population consists of two different strains of'}16. The method of claim 15 , wherein the CRISPR-associated enzyme is a Cas9 enzyme.17Streptococcus pyogenes. The method ...

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04-03-2021 дата публикации

SEQUENCE SPECIFIC ANTIMICROBIALS

Номер: US20210060141A1
Принадлежит:

Provided are compositions and methods for selectively reducing the amount of antibiotic resistant and/or virulent bacteria in a mixed bacteria population, or for reducing any other type of unwanted bacteria in a mixed bacteria population. The compositions and methods involve targeting bacteria that are differentiated from other members of the population by at least one unique clustered regularly interspaced short palindromic repeats (CRISPR) targeted DNA sequence. The compositions and methods can be readily adapted to target any bacteria or any bacteria plasmid, or both. 114.-. (canceled)15. A method for killing targeted pathogenic bacteria in a mixed bacterial population in a subject comprising:providing a pharmaceutical composition comprising a pharmaceutically acceptable carrier and packaged, recombinant phagemids that are packaged in phage capsids,wherein the packaged phagemids comprise a clustered regularly interspaced short palindromic repeats (CRISPR) system,wherein the CRISPR system comprises DNA encoding: i) a type II CRISPR-associated enzyme; and ii) a targeting RNA that targets at least one bacterial chromosome at a target site; andcontacting the bacterial population with the pharmaceutical composition by oral, parenteral, topical, nasal, or rectal administration to the subject;wherein the contacting with the pharmaceutical composition introduces at least some of the phagemids into at least some of the bacteria in the bacterial population,wherein subsequent to the introduction of the phagemids, the bacteria into which the phagemid is introduced expresses the targeting RNA and the type II CRISPR-associated enzyme,wherein the expressed type II CRISPR-associated enzyme cleaves the bacterial chromosome at the target site of the targeting RNA, andwherein the cleavage of the bacterial chromosome at the target site kills the targeted pathogenic bacteria.16. The method of claim 15 , wherein the CRISPR-associated enzyme is a Cas9 enzyme.17Streptococcus pyogenes. ...

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05-03-2015 дата публикации

Chimeric bacteriophage lysin with activity against staphylococci bacteria

Номер: US20150064156A1
Принадлежит: ROCKEFELLER UNIVERSITY

The present disclosure relates to chimeric bacteriophage lysins useful for the identification and/or reduction of staphylococcal populations. For example, a chimeric bacteriophage lysin was engineered and shown to effectively kill all strains of staphylococci tested including antibiotic resistant methicillin-resistant S. Aureus and VISA.

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05-03-2015 дата публикации

TUNING BACTERIOPHAGE HOST RANGE

Номер: US20150064770A1
Принадлежит: Massachusetts Institute of Technology

Various aspects and embodiments of the invention are directed to high-throughput phage-engineering methods and recombinant bacteriophages with tunable host ranges for controlling phage specificity.

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27-02-2020 дата публикации

MUTANTS OF THE BACTERIOPHAGE LAMBDA INTEGRASE

Номер: US20200063165A1
Принадлежит:

The present invention refers to lambda integrases comprising at least one amino acid mutation at positions and of the lambda integrase as set forth in SEQ ID NO: . The invention further refers to nucleic acid molecules comprising the nucleotide sequence encoding the mutant lambda integrase and to host cells containing these nucleic acid molecules. The invention also refers to methods of recombining a nucleic acid of interest into a target nucleic acid in the presence of the mutant lambda integrase and sequence specific recombination kits. 137-. (canceled)38. A lambda integrase mutant comprising the amino acid sequence of SEQ ID NO: 1 , except for amino acid mutations at least one position corresponding to residues 336 and 319 of the amino acid sequence of SEQ ID NO: 1.39. The lambda integrase mutant according to claim 38 , wherein the glutamate corresponding to position 319 of SEQ ID NO: 1 is replaced by glycine claim 38 , optionally wherein the aspartate corresponding to position 336 of SEQ ID NO: 1 is replaced by a hydrophobic amino acid claim 38 , optionally wherein the hydrophobic amino acid is an aliphatic amino acid claim 38 , optionally wherein the aliphatic amino acid is selected from the group consisting of isoleucine claim 38 , leucine and valine.40. The lambda integrase mutant according to claim 38 , wherein the aspartate corresponding to position 319 of SEQ ID NO: 1 is replaced by valine.41. The lambda integrase mutant according to claim 38 , wherein the glutamate corresponding to position 319 of SEQ ID NO: 1 is replaced by glycine and the aspartate corresponding to position 336 of SEQ ID NO 1 is replaced by valine.42. A nucleic acid molecule comprising a nucleotide sequence encoding a lambda integrase mutant comprising the amino acid sequence of SEQ ID NO: 1 claim 38 , except for amino acid mutations at least one position corresponding to residues 336 and 319 of the amino acid sequence of SEQ ID NO: 1.43. The nucleic acid molecule according to claim 42 ...

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24-03-2022 дата публикации

SCALABLE FERMENTATION PROCESS

Номер: US20220089648A1
Принадлежит:

This invention provides a robust fermentation process for the expression of a capsid protein of a bacteriophage which is forming a VLP by self-assembly, wherein the process is scalable to a commercial production scale and wherein the expression rate of the capsid protein is controlled to obtain improved yield of soluble capsid protein. This is achieved by combining the advantages of fed-batch culture and of lactose induced expression systems with specific process parameters providing improved repression of the promoter during the growth phase and high plasmid retention throughout the process. 1. A process for expression of a recombinant capsid protein of a RNA bacteriophage being capable of forming a virus-like particle (VLP) by self-assembly , said process comprising the steps of:a.) introducing an expression plasmid into a bacterial host, wherein said expression plasmid comprises an expression construct, wherein said expression construct comprises (i) a first nucleotide sequence encoding said recombinant capsid protein, or mutant or fragment thereof, and (ii) a promoter being inducible by lactose;b.) cultivating said bacterial host in a medium comprising a major carbon source;wherein said cultivating is performed in batch culture and under conditions under which said promoter is repressed by lacI, wherein said lacI is overexpressed by said bacterial host;c.) feeding said batch culture with said major carbon source; andd.) inducing said promoter with an inducer, wherein said feeding of said batch culture with said major carbon source is continued.2. (canceled)3. The process of claim 1 , wherein said bacteriophage is selected from the group consisting of:a.) bacteriophage Qβ;b.) bacteriophage AP205;c.) bacteriophage fr;d.) bacteriophage GA;e.) bacteriophage SP;f.) bacteriophage MS2;g.) bacteriophage M11;h.) bacteriophage MX1;i.) bacteriophage NL95;j.) bacteriophage f2;k.) bacteriophage PP7 andl.) bacteriophage R17.4. The process of claim 1 , wherein said RNA ...

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15-03-2018 дата публикации

COMPOSITIONS AND METHODS FOR SPECIFIC REACTIVATION OF HIV LATENT RESERVOIR

Номер: US20180073018A1
Принадлежит:

The present invention relates to compositions and methods for reactivation of HIV in vivo or in vitro. latently infected cell. In one embodiment, the present invention uses the CRISPR/Cas9 system in combination with the MS2 bacteriophage coat protein-mediated synergistic activation mediator (SAM) system to provide enhanced transcriptional activation of the HIV genome. 1. A composition for reactivation of a retrovirus in vitro or in vivo comprising: an isolated nucleic acid encoding a guide nucleic acid , wherein the guide nucleic acid comprises a targeting nucleotide sequence directed to one or more target sequences in the retroviral genome; an isolated nucleic acid encoding a Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated endonuclease/Cas (CRISPR/Cas) fusion protein , comprising CRISPR/Cas and one or more transcriptional activators; and , an isolated nucleic acid encoding a fusion protein comprising an RNA binding protein , fragments , mutants , derivatives or variants thereof and one or more transcriptional activators.2. The composition of claim 1 , wherein the CRISPR/Cas fusion protein comprises catalytically deficient Cas protein (dCas) claim 1 , orthologs claim 1 , homologs claim 1 , mutants variants or fragments thereof claim 1 , fused with one or more transcriptional activators.3. The composition of claim 1 , wherein the one or more target sequences comprises one or more sequences within a human immunodeficiency virus (HIV) LTR.4. The composition of claim 1 , wherein the RNA binding protein claim 1 , fragments claim 1 , mutants claim 1 , derivatives or variants thereof claim 1 , comprises a bacteriophage coat protein.5. The composition of claim 1 , wherein the one or more transcriptional activators comprise VP64 claim 1 , p65 claim 1 , HSF1 claim 1 , p65AD claim 1 , Rta claim 1 , Sp1 claim 1 , Vax claim 1 , GATA4 claim 1 , fragments claim 1 , mutants claim 1 , or any combinations thereof.6. The composition of claim 1 , wherein ...

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05-03-2020 дата публикации

PARTICLE FOR THE ENCAPSIDATION OF A GENOME ENGINEERING SYSTEM

Номер: US20200071720A1
Принадлежит:

The present invention relates to a retroviral particle comprising a protein derived from the Gag polyprotein, an envelope protein, optionally an integrase and at least two encapsidated non-viral RNAs, the encapsidated non-viral RNAs each comprising an RNA sequence of interest bound to an encapsidation sequence, each encapsidation sequence being recognized by a binding domain introduced into the protein derived from the Gag polyprotein and/or into the integrase, and at least one of said sequences of interest of the encapsidated non-viral RNAs comprises a part coding a nuclease. 1. Retroviral particle comprising a protein derived from the Gag polyprotein , an envelope protein , optionally an integrase and at least two encapsidated non-viral RNAs , the encapsidated non-viral RNAs each comprising an RNA sequence of interest bound to an encapsidation sequence , each encapsidation sequence being recognized by a binding domain introduced into the protein derived from the Gag polyprotein and/or into the integrase , and at least one of said sequences of interest of the encapsidated non-viral RNAs comprises a part coding a nuclease.2Natronobacterium gregoryi. Particle according to claim 1 , in which the nuclease is selected from the group constituted by the nucleases associated with the CRISPR system claim 1 , the nuclease of the TALEN system claim 1 , the nuclease of the Zn Finger system and the Argonaute (NgAgo) nuclease.3. Retroviral particle according to claim 1 , in which the sequence of interest of at least two encapsidated non-viral RNAs comprises a part coding a nuclease.4. Retroviral particle according to claim 1 , in which the at least two encapsidated non-viral RNAs differ by their sequence of interest.5. Retroviral particle according to claim 4 , in which:the sequence of interest of at least one RNA comprises a part coding a nuclease and a part coding a DNA recognition system at 3′, andthe sequence of interest of at least one RNA comprises a part coding a nuclease ...

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05-03-2020 дата публикации

EVOLUTION OF SITE-SPECIFIC RECOMBINASES

Номер: US20200071722A1

Some aspects of the present disclosure provide methods for evolving recombinases to recognize target sequences that differ from the canonical recognition sequences. Some aspects of this disclosure provide evolved recombinases, e.g., recombinases that bind and recombine naturally-occurring target sequences, such as, e.g., target sequences within the human Rosa26 locus. Methods for using such recombinases for genetically engineering nucleic acid molecules in vitro and in vivo are also provided. Some aspects of this disclosure also provide libraries and screening methods for assessing the target site preferences of recombinases, as well as methods for selecting recombinases that bind and recombine a non-canonical target sequence with high specificity. 1108.-. (canceled)109. A method for evolving a recombinase , the method comprising (1) the host cells are amenable to transfer of the phage vector;', '(2) the vector allows for expression of the recombinase in a host cell, can be replicated by the host cell, and the replicated vector can transfer from host cell to host cell;', '(3) the host cells express a gene product encoded by the at least one gene for the generation of infectious phage particles of (a) in response to the recombination of a recombinase target sequence by the recombinase, and the level of gene product expression depends on the activity of the recombinase towards the target sequence;, '(a) contacting a population of host cells with a population of phage vectors comprising a gene encoding a recombinase and deficient in at least one gene for the generation of infectious phage particles, wherein'}(b) incubating the population of host cells under conditions allowing for mutation of the gene encoding the recombinase and the transfer of the phage vectors from host cell to host cell, wherein host cells are removed from the host cell population, and the population of host cells is replenished with fresh host cells that do not harbor the phage vector;(c) ...

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14-03-2019 дата публикации

DETECTION AND IDENTIFICATION OF BACTERIA AND DETERMINATION OF ANTIBIOTIC SUSCEPTIBILITY USING BACTERIOPHAGE AND REPORTER MOLECULES

Номер: US20190078133A1
Принадлежит:

The present disclosure provides compositions and methods for identifying bacteria and profiling their antibiotic susceptibility. In particular, the methods and compositions of the present technology permit the detection of low concentrations of bacterial cells (e.g., <10 cells/ml) that are present within a complex biological sample. 1. A labelled detector bacteriophage (LDB) comprisinga capsid and nucleic acids wherein the capsid comprises an exterior surface relative to the nucleic acids of a phage; anda labelling moiety, wherein the labelling moiety is covalently linked to the exterior surface of the phage via an amide group or groups.2. The LDB of claim 1 , wherein the LDB comprises two or more labelling moieties claim 1 , wherein each labelling moiety is independently covalently linked to the exterior surface of the phage via an amide group or groups.6. The LDB of claim 1 , wherein the labelling moiety comprises one or more fluorescent moieties that are Atto Dye 590 claim 1 , Atto Dye 594 claim 1 , an amine-functionalized quantum dot claim 1 , a carboxylate-functionalized quantum dot claim 1 , fluorescein isothiocyanate (FITC) claim 1 , 4-acetamido-4′-isothiocyanatostilbene-2 claim 1 ,2′disulfonic acid; acridine and derivatives: acridine claim 1 , acridine isothiocyanate; Alexa Fluors: Alexa Fluor® 350 claim 1 , Alexa Fluor® 488 claim 1 , Alexa Fluor® 546 claim 1 , Alexa Fluor® 555 claim 1 , Alexa Fluor® 568 claim 1 , Alexa Fluor® 594 claim 1 , Alexa Fluor® 647 (Molecular Probes); 5-(2-aminoethyl)aminonaphthalene-1-sulfonic acid (EDANS); 4-amino-N-[3-vinylsulfonyl)phenyl]naphthalimide-3 claim 1 ,5 disulfonate (Lucifer Yellow VS); N-(4-anilino-1-naphthyl)maleimide; anthranilamide; Black Hole Quencher™ (BHQ™) dyes (biosearch Technologies); BODIPY dyes: BODIPY® R-6G claim 1 , BOPIPY® 530/550 claim 1 , BODIPY® FL; Brilliant Yellow; coumarin and derivatives: coumarin claim 1 , 7-amino-4-methylcoumarin (AMC claim 1 , Coumarin 120) claim 1 , 7-amino-4- ...

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24-03-2016 дата публикации

NOVEL BACTERIOPHAGE AND ANTIBACTERIAL COMPOSITION COMPRISING THE SAME

Номер: US20160083696A1
Принадлежит: CJ CHEILJEDANG CORPORATION

Provided is a novel bacteriophage ΦCJ20 (KCCM11362P). In addition, the present invention relates to an antibacterial composition including the bacteriophage ΦCJ20 (KCCM11362P) as an active ingredient. Further, the present invention is a method of preventing and/or treating infectious diseases by enterotoxigenic in animals except for humans using the bacteriophage ΦCJ20 (KCCM11362P) or the antibacterial composition containing the bacteriophage ΦCJ20 (KCCM11362P) as an active ingredient. 1Escherichia coli. A novel bacteriophage ΦCJ20 (KCCM11362P) having a specific bactericidal activity against enterotoxigenic (ETEC).2. A composition for preventing or treating an infectious disease caused by ETEC claim 1 , comprising the bacteriophage ΦCJ20 (KCCM11362P) of as an active ingredient.3. The composition according to claim 2 , wherein the infectious disease is colibacillosis.4. An antibiotic comprising the bacteriophage ΦCJ20 (KCCM11362P) of as an active ingredient.5. A feed additive or drinking water additive comprising the bacteriophage ΦCJ20 (KCCM11362P) of as an active ingredient.6. A disinfectant or cleaner comprising the bacteriophage ΦCJ20 (KCCM11362P) of as an active ingredient.7. A method of preventing or treating an infectious disease caused by ETEC claim 1 , comprising administering the bacteriophage ΦCJ20 (KCCM11362P) of to animals except for humans.8. The method according to claim 7 , wherein the infectious disease is colibacillosis.9. A method of preventing or treating an infectious disease caused by ETEC claim 2 , comprising administering the composition of to animals except for humans.10. The method according to claim 9 , wherein the infectious disease is colibacillosis. The present invention relates to a novel bacteriophage having a specific bactericidal activity against Enterotoxigenic (ETEC), and an antibacterial composition comprising the same. In addition, the present invention relates to a method of preventing or treating animal diseases using the novel ...

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24-03-2016 дата публикации

NOVEL BACTERIOPHAGE AND ANTIBACTERIAL COMPOSITION COMPRISING THE SAME

Номер: US20160083697A1
Принадлежит:

Provided is a novel bacteriophage ΦCJ20 (KCCM11362P). In addition, the present invention relates to an antibacterial composition including the bacteriophage ΦCJ20 (KCCM11362P) as an active ingredient. Further, the present invention is a method of preventing and/or treating infectious diseases by enterotoxigenic in animals except for humans using the bacteriophage ΦCJ20 (KCCM11362P) or the antibacterial composition containing the bacteriophage ΦCJ20 (KCCM11362P) as an active ingredient. 1Escherichia coli. A novel bacteriophage ΦCJ20 (KCCM11362P) having a specific bactericidal activity against enterotoxigenic (ETEC).2. A composition for preventing or treating an infectious disease caused by ETEC claim 1 , comprising the bacteriophage ΦCJ20 (KCCM11362P) of as an active ingredient.3. The composition according to claim 2 , wherein the infectious disease is colibacillosis.4. An antibiotic comprising the bacteriophage ΦCJ20 (KCCM11362P) of as an active ingredient.5. A feed additive or drinking water additive comprising the bacteriophage ΦCJ20 (KCCM11362P) of as an active ingredient.6. A disinfectant or cleaner comprising the bacteriophage ΦCJ20 (KCCM11362P) of as an active ingredient.7. A method of preventing or treating an infectious disease caused by ETEC claim 1 , comprising administering the bacteriophage ΦCJ20 (KCCM11362P) of to animals except for humans.8. The method according to claim 7 , wherein the infectious disease is colibacillosis.9. A method of preventing or treating an infectious disease caused by ETEC claim 2 , comprising administering the composition of to animals except for humans.10. The method according to claim 9 , wherein the infectious disease is colibacillosis. The present invention relates to a novel bacteriophage having a specific bactericidal activity against Enterotoxigenic (ETEC), and an antibacterial composition comprising the same. In addition, the present invention relates to a method of preventing or treating animal diseases using the novel ...

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31-03-2022 дата публикации

METHOD FOR TREATMENT AND CONTROL OF PLANT DISEASE

Номер: US20220098543A1
Принадлежит:

Methods and compositions are provided for preventing or reducing symptoms or disease associated with Xylella fastidiosa or Xanthomonas axonopodis in a plant. The invention provides novel bacteriophages virulent to Xylella fastidiosa or Xanthomonas axonopodis, including XfaMija and XfaMijo, and further provides methods for treating or preventing Pierce's Disease or Citrus Canker in plants. 122-. (canceled)23X. fastidiosaXanthomonas. A method of propagating a virulent bacteriophage that includes in its host range , comprising infecting a culture of bacteria with said virulent bacteriophage , allowing said bacteriophage to propagate , and isolating virulent bacteriophage particles from the culture.24. The method of claim 23 , wherein the bacteriophage infects the cell by binding to a cell surface feature.25. The method of claim 23 , wherein said cell surface feature is a Type IV pilus.26. The method of claim 23 , wherein said virulent bacteriophage comprises a tailed bacteriophage from the group consisting of a podophage claim 23 , a siphophage claim 23 , and a myophage.27. The method of claim 23 , wherein said virulent bacteriophage is isolated from the environment.28. The method of claim 23 , wherein the bacteriophage is isolated from a sewage treatment plant or effluent therefrom.29. The method of claim 23 , wherein the bacteriophage is isolated from a plant or a surface thereof or from the surrounding soil.30. The method of claim 23 , wherein a surrogate host is used to enrich for virulent bacteriophage.31Xylella fastidiosa.. The method of claim 23 , wherein the bacteriophage is virulent in32. The method of claim 23 , further comprising the use of agar overlaying for growth of the bacteriophage.33Xanthomonas. The method of claim 23 , wherein the culture of bacteria comprises species strain EC-12 claim 23 , a representative sample having been deposited under ATCC Accession Number PTA-13101.34. The method of clam 23 claim 23 , wherein the bacteriophage is selected ...

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25-03-2021 дата публикации

COMPOSITIONS OF AND METHODS FOR IN VITRO VIRAL GENOME ENGINEERING

Номер: US20210087538A1
Принадлежит:

The present disclosure relates to a method of in vitro engineering of nucleic acids. This disclosure further relates to in vitro engineering of viral genomes and to the improvement of viral properties by in vitro genomic engineering of viral genomes. Specifically, the disclosure relates to in vitro viral genomic digestion using RNA-guided Cas9, the assembly of a recombinant genome by the insertion of a DNA or RNA fragment into the digested viral genome and transformation of a host cell with the recombinant genome. This method also related to in vitro engineering for error correction of nucleic acids. 1. An engineered virus comprising an engineered viral nucleic acid capable, upon introduction into a host cell, of producing non-naturally occurring viral particles with two or more improved viral properties compared to the viral particles produced by introduction of the non-engineered viral nucleic acid into a host cell. This application is a continuation of U.S. Non-Provisional patent application Ser. No. 16/374,646 filed Apr. 3, 2019 which is a continuation of U.S. Ser. No. 16/246,381 filed Jan. 11, 2019 issued as U.S. Pat. No. 10,711,253, which is a continuation of U.S. Non-Provisional patent application Ser. No. 14/970,458 filed Dec. 15, 2015 issued as U.S. Pat. No. 10,221,398, which is a continuation of International Patent Application No. PCT/US2015/065891 filed Dec. 15, 2015, which claims priority to U.S. Provisional Patent Application No. 62/092,707 filed Dec. 16, 2014, to U.S. Provisional Patent Application No. 62/102,362 filed Jan. 12, 2015, and to U.S. Provisional Patent Application No. 62/242,811 filed Oct. 16, 2015, the contents of all of which are hereby incorporated by reference in their entireties.A Sequence Listing is provided herewith as a text file, “054249-514C04US_SequenceListing_ST25.txt” created on Nov. 25, 2020 and having a size of 143,050 bytes. The contents of the text file are incorporated by reference herein in their entirety.The disclosure ...

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21-03-2019 дата публикации

BACTERIOPHAGE-POLYMER HYBRID

Номер: US20190083610A1
Принадлежит: IMPERIAL INNOVATIONS LIMITED

The invention provides a targeted bacteriophage-polymer complex comprising a recombinant targeted-bacteriophage and a cationic polymer. The complex has a net positive charge. The invention provides methods of preparing bacteriophages and complexes thereof, and to their uses for the delivery of transgenes in a variety of gene therapy applications. 133-. (canceled)34. A method of delivering a transgene to a mammalian cell , comprising:administering to a mammalian cell a targeted bacteriophage-polymer complex comprising a recombinant negatively charged targeted-bacteriophage and a cationic polymer selected from the group consisting of poly-D-lycine (PDL), diethylaminoethyl-dextran (DEAE.DEX) and polyethyleneimine (PEI), wherein the recombinant bacteriophage comprises a nucleic acid sequence, which encodes a protein ligand that is capable of being expressed on the capsid coat of the recombinant bacteriophage, and which is specific for a protein expressed on a mammalian target cell or tissue, so as to enable targeted delivery thereto, wherein the complex has a net positive charge and a ζ-potential of at least 5 mV at physiological pH, and wherein the complex comprises a weight:weight ratio of about 100 ng to 400 ng polymer:1 μg phage.35. The method of claim 34 , wherein the bacteriophage comprises a transgene claim 34 , which exerts a therapeutic effect on a target cell claim 34 , wherein the transgene comprises the Herpes simplex virus tyrosine kinase gene.36. The method of claim 34 , wherein the bacteriophage comprises a transgene claim 34 , which exerts a therapeutic effect on a target cell claim 34 , wherein the transgene comprises the Herpes simplex virus tyrosine kinase gene.37. The method of claim 34 , wherein the bacteriophage is F1 claim 34 , Fd or M13.38. The method of claim 34 , wherein the cationic polymer comprises DEAE.DEX.39. The method of claim 34 , wherein the polymer comprises PDL.40. The method of claim 34 , wherein the complex comprises a weight: ...

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21-03-2019 дата публикации

Protein variants for use as lipid bilayer-integrated nanopore, and methods thereof

Номер: US20190085031A1
Автор: Peixuan Guo, Shaoying Wang

The presently-disclosed subject matter relates to an engineered T3 or T4 viral DNA-packaging motor connector protein that can be incorporated into a lipid membrane to form an electroconductive aperture, and which can be provided for other uses described herein.

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12-05-2022 дата публикации

SEQUENCE SPECIFIC ANTIMICROBIALS

Номер: US20220143154A1
Принадлежит:

Provided are compositions and methods for selectively reducing the amount of antibiotic resistant and/or virulent bacteria in a mixed bacteria population, or for reducing any other type of unwanted bacteria in a mixed bacteria population. The compositions and methods involve targeting bacteria that are differentiated from other members of the population by at least one unique clustered regularly interspaced short palindromic repeats (CRISPR) targeted DNA sequence. The compositions and methods can be readily adapted to target any bacteria or any bacteria plasmid, or both. 1. (canceled)2. A pharmaceutical composition for killing targeted bacteria in a mixed bacterial population comprising:a pharmaceutically acceptable carrier and a clustered regularly interspaced short palindromic repeats (CRISPR) system packaged in a phage,wherein the CRISPR system comprises DNA encoding:i) a Type I, Type II, or Type III CRISPR-associated enzyme; andii) a targeting RNA that targets at least one bacterial chromosome at a target site; andwherein, upon contacting a bacterial population containing the at least one bacterial chromosome with the pharmaceutical composition, the CRISPR system is introduced into bacteria in the bacterial population, wherein subsequent to the introduction of the CRISPR system, the targeting RNA and the CRISPR-associated enzyme are expressed in the bacteria into which the CRISPR system is introduced,wherein the expressed CRISPR-associated enzyme cleaves the bacterial chromosome at the target site of the targeting RNA, and wherein the cleavage of the bacterial chromosome at the target site kills the bacteria.3. The pharmaceutical composition of claim 2 , wherein the phage can infect different types of bacteria in a mixed bacteria population.4Streptococcus, Staphylococcus, Clostridium, Bacillus, Salmonella, Helicobacter pylori, Neisseria gonorrhoeae, Neisseria meningitidis,Escherichia coli.. The pharmaceutical composition of claim 2 , wherein the phage is ...

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05-04-2018 дата публикации

Therapeutic Cancer Vaccine Targeted to HAAH (Aspartyl-[Asparaginyl]-Beta-Hydroxylase

Номер: US20180092969A1
Принадлежит:

The present invention encompasses a cancer vaccine therapy targeting Aspartyl-[Asparaginyl]-,8-hydroxylase (HAAH). The present invention contemplate bacteriophage expressing HAAH peptide fragments and methods for using said bacteriophage in methods of treating cancer. 1. A bacteriophage comprising at least one amino acid sequence native to Aspartyl-[Asparaginyl]-{3-hydroxylase.2. The bacteriophage of claim 1 , wherein the at least one amino acid sequence native to Aspartyl-[Asparaginyl]-{3-hydroxylase is selected from the group consisting of the amino acid sequence of Construct I.3. The bacteriophage of claim 1 , wherein the bacteriophage comprises the amino acid sequence of Construct II.4. The bacteriophage of claim 1 , wherein the bacteriophage comprises the amino acid sequence of Construct III.5. The bacteriophage of claim 1 , wherein the bacteriophage is selected from the group consisting of Lambda claim 1 , T4 claim 1 , T7 claim 1 , and M13/fl.6. The bacteriophage of claim 5 , wherein the bacteriophage is bacteriophage Lambda.7. A method for treating cancer comprising the step of providing a patient with an immune system stimulating amount of the bacteriophage of .8. A nucleic acid construct comprising at least one nucleotide sequence encoding an amino acid sequence native to Aspartyl-[Asparaginyl]- claim 1 ,8-hydroxylase and a nucleotide sequence encoding gpD.9. The nucleic acid construct of claim 8 , wherein the at least one amino acid sequence native to Aspartyl-[Asparaginyl]- claim 8 ,8-hydroxylase is the amino acid sequence of Construct I.10. The nucleic acid construct of claim 8 , wherein the at least one amino acid sequence native to Aspartyl-[Asparaginyl]- claim 8 ,8-hydroxylase is the amino acid sequence of Construct II.11. The nucleic acid construct of claim 8 , wherein the at least one amino acid sequence native to Aspartyl-[Asparaginyl]- claim 8 ,8-hydroxylase is the amino acid sequence of Construct III.12. A recombinant Lambda phage comprising the ...

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05-04-2018 дата публикации

ADSORPTIVE MEMBRANES FOR TRAPPING VIRUSES

Номер: US20180094247A1
Автор: Etzel Mark R.
Принадлежит: WISCONSIN ALUMNI RESEARCH FOUNDATION

A disposable, virus-trapping membrane, and a corresponding method to remove viruses from solution are described. The membrane includes a disposable, micro-porous filter membrane and a ligand immobilized on the membrane. The ligand irreversibly and selectively binds viruses. The ligand also has a pKa sufficiently high to repel antibodies via electrostatic charge repulsion. 122-. (canceled)23. A disposable , virus-trapping membrane comprising:a disposable, micro-porous filter membrane; anda multi-modal anion-exchange ligand that has a pKa sufficiently high to repel basic proteins via electrostatic charge repulsion immobilized on the filter membrane, wherein the ligand comprises one or more of tyrosinol, tryptophanol, octopamine, 1,3-diamino-2-hydroxypropane, tris(2-aminoethyl)amine, and agmatine, (a) binds neutral viruses; and', '(b) yields a log-reduction value (LRV) of at least 1.0 for the neutral viruses disposed in a solution comprising 50 mM salt., 'wherein the virus-trapping membrane24. The virus-trapping membrane of claim 23 , wherein the ligand comprises one or more of tryptophanol claim 23 , tris(2-aminoethyl)amine claim 23 , and agmatine claim 23 , and wherein the virus-trapping membrane is dimensioned and configured to yield a log-reduction value (LRV) of at least 1.0 for neutral viruses disposed in a solution comprising 150 mM salt.25. The virus-trapping membrane of claim 23 , wherein the ligand comprises one or more of tris(2-aminoethyl)amine and agmatine claim 23 , and wherein the virus-trapping membrane is dimensioned and configured to yield a log-reduction value (LRV) of at least 5.0 for neutral viruses disposed in a solution comprising 50 mM salt.26. The virus-trapping membrane of claim 23 , wherein the ligand comprises one or more of tris(2-aminoethyl)amine and agmatine claim 23 , and wherein the virus-trapping membrane is dimensioned and configured to yield a log-reduction value (LRV) of at least 5.0 for neutral viruses disposed in a solution ...

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12-05-2022 дата публикации

METHODS AND COMPOSITIONS FOR INCREASED DOUBLE STRANDED RNA PRODUCTION

Номер: US20220145294A1
Принадлежит: APSE, INC.

The invention provides methods and compositions for improved production of large quantities of unencapsidated double strand RNA (dsRNA) in vivo. The disclosed methods and compositions, comprising co-expression of genes encoding orotate phosporibosyl transferase, bacteriophage coat protein and dsRNA produce a significant improvement over current in vivo methods of producing unencapsidated dsRNA. 1. A method for producing unencapsidated dsRNA in a microbial cell , comprising the step of co-expressing in the microbial cell the dsRNA and a coat protein gene encoding a capsid protein.2. The method of claim 1 , wherein the capsid protein is encoded by a leviviridae coat protein gene.3. The method of claim 1 , wherein the capsid protein is encoded by the coat protein gene of bacteriophage MS2 or the coat protein gene of bacteriophage Qβ.4. The method of claim 1 , wherein the gene encoding the dsRNA and the coat protein gene encoding the capsid protein are expressed from an inducible promoter.5. The method of claim 4 , wherein the coat protein gene encoding the capsid protein is expressed from a constitutive promoter and the gene encoding the dsRNA is expressed from an inducible promoter.6. The method of claim 1 , wherein the coat protein gene encoding the capsid protein is expressed prior to or concomitant with the gene encoding the dsRNA.7. The method of claim 1 , wherein the gene encoding the dsRNA and the coat protein gene encoding the capsid protein are present on one plasmid or extrachromosomal element within the microbial cell.8. The method of claim 1 , wherein the dsRNA is an RNAi precursor.9. The method of claim 1 , wherein after producing the dsRNA the microbial cell is subsequently lysed and the dsRNA purified from the lysate prior to processing for application.10. The method of claim 1 , wherein after producing the dsRNA the microbial cell is lysed and processed for application without further purification of the dsRNA.11. The method of claim 1 , wherein after ...

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28-03-2019 дата публикации

Methods and Compositions for Increased Double Stranded RNA Production

Номер: US20190093108A1
Принадлежит: APSE, INC.

Methods and materials for improved in vivo production of dsRNA are presented. Yields of dsRNA are significantly increased in the presence of capsid protein. The improved yield of dsRNA is not dependent on the presence of specific cognate binding sites for capsid protein associated with the dsRNA, but is dependent on capsid protein. 1. A method for producing unencapsidated dsRNA in a microbial cell , comprising the step of co-expressing in the microbial cell the dsRNA and a coat protein gene encoding a capsid protein.2. The method of claim 1 , wherein the capsid protein is encoded by a leviviridae coat protein gene.3. The method of claim 1 , wherein the capsid protein is encoded by the coat protein gene of bacteriophage MS2.4. The method of claim 1 , wherein the capsid protein is encoded by the coat protein gene of bacteriophage Qβ.5. The method of claim 1 , wherein the gene encoding the dsRNA and the coat protein gene encoding the capsid protein are expressed from an inducible promoter.6. The method of claim 5 , wherein the coat protein gene encoding the capsid protein is expressed from a constitutive promoter and the gene encoding the dsRNA is expressed from an inducible promoter.7. The method of claim 1 , wherein the coat protein gene encoding the capsid protein is expressed prior to or concomitant with the gene encoding the dsRNA.8. The method of claim 1 , wherein the gene encoding the dsRNA and the coat protein gene encoding the capsid protein are present on one plasmid or extrachromosomal element within the microbial cell.9. The method of claim 1 , wherein the gene encoding the dsRNA and the coat protein gene encoding the capsid protein are present on separate plasmids or extrachromosomal elements within the microbial cell.10. The method of claim 1 , wherein one of the genes encoding the dsRNA and the capsid protein are present on a plasmid or extrachromosomal element and the other of the genes encoding the dsRNA and the capsid protein are present on the ...

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16-04-2015 дата публикации

SCALABLE FERMENTATION PROCESS

Номер: US20150104827A1
Принадлежит: Cytos Biotechnology AG

This invention provides a robust fermentation process for the expression of a capsid protein of a bacteriophage which is forming a VLP by self-assembly, wherein the process is scalable to a commercial production scale and wherein the expression rate of the capsid protein is controlled to obtain improved yield of soluble capsid protein. This is achieved by combining the advantages of fed-batch culture and of lactose induced expression systems with specific process parameters providing improved repression of the promoter during the growth phase and high plasmid retention throughout the process. 1. A process for expression of a recombinant capsid protein of a RNA bacteriophage being capable of forming a VIP by self-assembly , said process comprising the steps of:a.) introducing an expression plasmid into a bacterial host, wherein said expression plasmid comprises an expression construct, wherein said expression construct comprises (i) a first nucleotide sequence encoding said recombinant capsid protein, or mutant or fragment thereof, and (ii) a promoter being inducible by lactose;b.) cultivating said bacterial host in a medium comprising a major carbon source; wherein said cultivating is performed in batch culture and under conditions under which said promoter is repressed by lac, wherein said lacI is overexpressed by said bacterial host;c.) feeding said batch culture with said major carbon source; andd.) inducing said promoter with an inducer, wherein said feeding of said batch culture with said major carbon source is continued.2. (canceled)3. The process of claim 1 , wherein said bacteriophage is selected from the group consisting of:a.) bacteriophage Qβ;b.) bacteriophage AP205;c.) bacteriophage fr;d.) bacteriophage GA;e.) bacteriophage SP;f.) bacteriophage MS2;g.) bacteriophage M11;h.) bacteriophage MX1;i.) bacteriophage NL95;j.) bacteriophage f2;k.) bacteriophage PP7 andl.) bacteriophage R17.4. The process of claim 1 , wherein said RNA bacteriophage is Qβ.5. The ...

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14-04-2016 дата публикации

NOVEL PEPTIDE SELECTIVELY BINDING TO VOLATILE ORGANIC COMPOUNDS

Номер: US20160103108A1
Принадлежит:

Provided is a peptide selectively binding to a volatile organic compound, in which the peptide has excellent selectivity for the volatile organic compound and has stability at room temperature so as to effectively collect and detect or eliminate the volatile organic compound. 1. A peptide or peptide set , comprising one or more selected from the group consisting of amino acid sequences of RXXSSXP (SEQ ID NO. 1) , XSSPXGA (SEQ ID NO. 2) , SKXSPXT (SEQ ID NO. 3) , XXSSXMA (SEQ ID NO. 4) , XXSGXAA (SEQ ID NO. 5) , XTSSAXP (SEQ ID NO. 6) , RXTXSXS (SEQ ID NO. 7) , TXXTXXG (SEQ ID NO. 8) , XXGTASS (SEQ ID NO. 9) , AGXXSSA (SEQ ID NO. 10) , XSSPXGA (SEQ ID NO. 11) , SGTXXGP (SEQ ID NO. 12) , SRXXXMX(SEQ ID NO. 13) , XPXPTXP (SEQ ID NO. 14) , GXMMAAP (SEQ ID NO. 15) , and XSAXPXP (SEQ ID NO. 16).2. The peptide or peptide set of claim 1 , wherein the peptide or peptide set selectively binds to volatile organic compounds.3. The peptide or peptide set of claim 2 , wherein the volatile organic compounds are hydrocarbons having a benzene ring.4. The peptide or peptide set of claim 1 , wherein the peptide or peptide set comprises one or more selected from the group consisting of amino acid sequences of SEQ ID NOS. 17 to 32.5. The peptide or peptide set of claim 1 , wherein the peptide or peptide set is displayed on a coat protein of a phage or a fragment thereof.6. The peptide or peptide set of claim 5 , wherein the phage is M13 phage claim 5 , F1 phage claim 5 , Fd phage claim 5 , If1 phage claim 5 , Ike phage claim 5 , Zj/Z phage claim 5 , Ff phage claim 5 , Xf phage claim 5 , Pf1 phage claim 5 , or Pf3 phage.7. The peptide or peptide set of claim 5 , wherein the C-terminus of the peptide or peptide set is linked to the N-terminus of the coat protein of the phage claim 5 , or the peptide or peptide set is inserted between consecutive amino acid sequences of the coat protein of the phage or replaces the consecutive amino acid sequences of the coat protein.8. The peptide or ...

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08-04-2021 дата публикации

On-Chip Nanoscale Storage System Using Chimeric DNA

Номер: US20210103824A1
Принадлежит:

The present disclosure provides systems and methods that can provide portable, real-time accessible DNA memories. An example DNA-based data storage system includes a loading region configured to receive a plurality of DNA-based data storage elements in a suspension fluid and a plurality of microtubes disposed in a capture/release region. The microtubes are configured to capture and release the DNA-based data storage elements. The DNA-based data storage system also includes a linearization region configured to linearize the DNA-based data storage elements and a readout region with a readout device configured to provide information indicative of the respective DNA-based data storage elements. 1. A deoxyribonucleic acid (DNA)-based data storage element comprising:a DNA backbone; anda plurality of non-natural nucleic acids bioconjugated to the DNA backbone.2. The DNA-based data storage element of claim 1 , wherein at least one of the non-natural nucleic acids comprise a peptide nucleic acid (PNA).3. The DNA-based data storage element of claim 2 , wherein the PNA comprises a peptide backbone and a plurality of natural nucleobase monomers.4. The DNA-based data storage element of claim 1 , wherein the DNA backbone comprises single-stranded DNA.5. The DNA-based data storage element of claim 1 , wherein the DNA backbone comprises double-stranded DNA.6. The DNA-based data storage element of claim 1 , wherein the plurality of non-natural nucleic acids comprises a structurally-defined branched polymer architecture.7. A microfluidic deoxyribonucleic acid (DNA)-based data storage system claim 1 , comprising:a loading region configured to receive a plurality of DNA-based data storage elements in a suspension fluid;a plurality of microtubes disposed in a capture/release region, wherein the microtubes are configured to capture and release the DNA-based data storage elements;a linearization region configured to linearize the DNA-based data storage elements; anda readout region with a ...

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04-04-2019 дата публикации

Phage-based detection method for antimicrobial susceptibility testing and identification of bacterial species

Номер: US20190100811A1
Принадлежит: Guild Associates Inc, Quidel Corp

Methods for determining bacterial identity and susceptibility or resistance to antibiotic or antimicrobial agents are provided. In one embodiment, the bacteria is cultured in the presence or absence or the antibiotic agent to generate a plurality of primary cultures, which are then cultured in the presence or absence of transforming phages to generate a first secondary culture that comprise transformed bacteria that have been treated with the antibiotic agent and a second secondary culture that comprises transformed bacteria that have not been treated with the antibiotic agent. The recombinant phages are specific to the bacteria and comprise a heterologous marker. The susceptibility or resistance of the bacteria to the antibiotic or antimicrobial agent is determined by comparing a level or activity of the marker in the first and second secondary cultures.

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23-04-2015 дата публикации

FILAMENTOUS BACTERIOPHAGE AS AN ANGIOGENESIS MODULATOR

Номер: US20150110745A1
Автор: Dor-On Eyal, SOLOMON Beka
Принадлежит:

The invention relates to a filamentous bacteriophage, carrying bacterial Lipopolysaccharide (LPS) endotoxin on its surface, for use in treating cancer and in inhibiting angiogenesis, and in a different context, for use in promoting angiogenesis in diseases or conditions in which there is insufficient angiogenesis. 113-. (canceled)14. A method for treating cancer or for inhibiting angiogenesis in vascular endothelium characterized by a non-resting , stressed state and excessive angiogenesis , comprising administering to a patient in need thereof an effective amount of a filamentous bacteriophage carrying bacterial Lipopolysaccharide (LPS) endotoxin on its surface , optionally displaying on its surface a peptide that binds to Tie2 receptor tyrosine kinase , with the proviso that the filamentous bacteriophage does not display an antibody or a tumor specific peptide.15. (canceled)16. A method for promoting angiogenesis in a disease or condition in which there is insufficient angiogenesis , comprising administering to a patient in need thereof an effective amount of a filamentous bacteriophage carrying bacterial Lipopolysaccharide (LPS) endotoxin on its surface , optionally displaying on its surface a peptide that binds to Tie2 receptor tyrosine kinase , with the proviso that the filamentous bacteriophage does not display vascular endothelial growth factor (VEGF).17. The method of claim 14 , wherein the filamentous bacteriophage is a wild type claim 14 , a wild type-like or a naturally occurring filamentous bacteriophage.18. The method of claim 14 , wherein the filamentous bacteriophage is selected from the group consisting of M13 claim 14 , fl claim 14 , fd and mixtures thereof.19. The method of claim 14 , wherein the filamentous bacteriophage is administered by intranasal administration.20. The method of claim 14 , wherein the amount of bacterial LPS endotoxin carried on the filamentous bacteriophage is more than 100 endotoxin units/2×10bacteriophage or more than about ...

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19-04-2018 дата публикации

Disease control of the plant bacterial pathogens causing citrus canker and rice blight

Номер: US20180105801A1
Автор: Ting-Yu Yeh
Принадлежит: Auxergen, Auxergen Inc

The present invention describes applications and methods (1) to use bacteriophage Cf and its variants to prevent and treat the citrus canker pathogen, Xanthomonas citri subsp. citri; (2) to engineer recombinant Cf phages that the infectivity is controllable without being harmful to the rest of environment; (3) to engineer and produce recombinant Cf phages with longer storage shelf life; (4) to use Cf phage as a vector for the introduction and insertion of foreign genetic material into Xanthomonas citri subsp. citri. genome; (5) to use and engineer Xp12 and Xf bacteriophages to inhibit Xanthomonas oryzae pv. oryzae, the causal agent of the rice blight disease.

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02-04-2020 дата публикации

DNA ORIGAMI NANOSTRUCTURES FOR TREATMENT OF ACUTE KIDNEY INJURY

Номер: US20200101101A1
Принадлежит:

Disclosed herein are methods of treating acute kidney injury. The A method can include administering a sufficient amount of a DNA origami nanostructure to a subject afflicted with AKI to increase an excretory function of said subject. In some examples, the DNA origami nanostructure includes a scaffold strand and a plurality of staple strands, in which the scaffold strand comprises a M1 3 viral genome having a length of 7249 base pairs; and each staple strand of the plurality of staple strands has a length of about 20 to 60 base pairs. 1. A method of treating acute kidney injury (AKI) , the method comprising administering an effective amount of a DNA origami nanostructure to a subject afflicted with AKI to increase an excretory function of said subject.2. The method of claim 1 , wherein the DNA origami nanostructure comprises a scaffold strand and a plurality of staple strands claim 1 , wherein:the scaffold strand comprises a M13 viral genome having a length of 7249 base pairs; andeach staple strand of the plurality of staple strands has a length of about 20 to 60 base pairs.3. The method of claim 2 , further comprising providing sufficient conditions to induce a self-assembly of the scaffold strand and the plurality of staple strands into one of a plurality of forms.4. The method of claim 3 , wherein the DNA origami nanostructure comprises a rectangular DNA origami nanostructure.5. The method of claim 3 , wherein the DNA origami nanostructure comprises a triangular DNA origami nanostructure.6. The method of claim 3 , wherein the DNA origami nanostructure comprises a tubular DNA origami nanostructure.7. The method of claim 2 , further comprising determining whether the excretory function of the subject is increased by measuring a plurality of end products of nitrogen metabolism in a blood sample of the subject.8. The method of claim 7 , wherein the plurality of end products comprises urea and creatinine.9. The method of claim 2 , further comprising reducing an amount ...

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26-04-2018 дата публикации

MECHANISMS OF ANTIMICROBIAL SUSCEPTIBILITY6

Номер: US20180112281A1
Принадлежит:

Disclosed herein are methods and compositions for determining the presence or absence of a mechanism of antimicrobial resistance in a sample. 1. A kit for determining a mechanism of antimicrobial resistance for a microorganism to an antimicrobial agent comprising:an antimicrobial agent, wherein the antimicrobial agent is a compound that kills, inhibits the growth of, or otherwise compromises the viability of the growth of one or more microorganisms;a non-replicative transduction particle (NRTP) comprising a reporter nucleic acid molecule encoding a reporter molecule;a caged substrate capable of entering the microorganism and becoming an un-caged substrate in the presence of an enzyme related to a mechanism of resistance to the antimicrobial agent, wherein the un-caged substrate reacts with the reporter molecule to produce a detectable signal, wherein detection of the detectable signal confirms a presence of the microorganism in the sample; andinstructions for using the antimicrobial agent, the NRTP, and the caged substrate to determine the mechanism of antimicrobial resistance for the microorganism to the antimicrobial agent based on the presence or absence of a detectable indication of viability associated with the microorganism when the microorganism is in contact with the antimicrobial agent, the NRTP and the caged substrate, wherein the presence of a detectable indication of viability indicates that the microorganism is viable and that the enzyme related to the mechanism of resistance to the antimicrobial agent is expressed by the microorganism, and wherein the absence of an indication of viability indicates that the microorganism is not viable and that the enzyme related to the mechanism of resistance to the antimicrobial agent is not expressed by the microorganism.2. The kit of claim 1 , wherein said reporter molecule is expressed from a reporter gene wherein said reporter gene is selected from the group consisting of genes encoding enzymes mediating ...

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07-05-2015 дата публикации

BACTERIOPHAGE FOR BIOCONTROL OF SALMONELLA AND IN THE MANUFACTURING OR PROCESSING OF FOODS

Номер: US20150125424A1
Принадлежит: Micreos B.V.

The invention relates to the field of microbiology, specifically to a bacteriophage, polypeptide and a corresponding polynucleotide, a nucleic acid molecule and/or vector and/or cell comprising such polynucleotide, a composition comprising said bacteriophage, polypeptide, polynucleotide, construct, vector and/or cell, preferably for preventing, treating or diagnosing contamination with and/or a condition in an individual related to The invention further relates to an antimicrobial composition for medical use or for use as a food additive or as a disinfectant, or for detecting bacteria, preferably in a diagnostic application, wherein said antimicrobial composition comprises a bacteriophage, polypeptide, corresponding polynucleotide, construct and/or vector and/or cell comprising such polypeptide and/or composition according to the present invention. 1. A composition comprising an isolated bacteriophage belonging to the morphotype group of the Myoviridae , comprising at least one feature selected from the group consisting of:the genome of the bacteriophage is at least 100 kbp,the genome of the bacteriophage comprises at least one polynucleotide encoding a polypeptide with an amino acid sequence having at least 70% sequence identity with an amino acid sequence selected from the group consisting of SEQ ID NO: 3, 5, 7, 9 and 11,{'i': 'Salmonella', 'the bacteriophage receptor is outer membrane protein C,'}{'i': 'Salmonella', 'the bacteriophage can infect and lyse at least one species.'}2. The composition according to claim 1 , the isolated bacteriophage being Phage S16 claim 1 , deposit number CBS130493.36-. (canceled)7. The composition according to claim 1 , wherein said composition is an antimicrobial.8. The composition according to claim 1 , further comprising an additional active ingredient selected from the group consisting of: a further bacteriophage claim 1 , a bacteriostatic agent claim 1 , a bactericide agent claim 1 , an antibiotic claim 1 , a surfactant and an ...

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05-05-2016 дата публикации

RECOMBINANT PHAGE AND METHODS

Номер: US20160122729A1
Принадлежит:

This disclosure provided methods of cloning a phage genome. Also provided are methods of making a recombinant phage genome. In some embodiments the phage genome is engineered to comprise a heterologous nucleic acid sequence, for example a sequence comprising an open reading frame. In some embodiments the phage genome is cloned in a yeast artificial chromosome. Recombinant phage genomes and recombinant phage are also provided. In some embodiments the methods are high throughput methods such as methods of making aa plurality of recombinant phage genomes or recombinant phage. Collections of recombinant phage genomes and recombinant phage are also provided. 2. A method of making a recombinant phage genome , comprising:providing vector host cells comprising a recombinant vector comprising a cloned phage genome;inserting a heterologous nucleic acid sequence into the starting phage genome to provide a recombinant phage genome; andselecting vector host cells comprising the recombinant vector comprising the recombinant phage genome to thereby provide the cloned phage genome. This is a continuation of U.S. patent application Ser. No. 13/627,060, filed on Sep. 26, 2012, allowed, which in turn claims priority to U.S. Provisional Patent Application No. 61/539,454, filed Sep. 26, 2011; U.S. Provisional Patent Application No. 61/549,743, filed Oct. 20, 2011; and U.S. Provisional Patent Application No. 61/642,691, filed May 4, 2012. The entire contents of each of those applications are hereby incorporated herein by reference.The contents of the text file named “SAM6-006_C01US 320350-2055_ST25.txt”, which was created on Jan. 7, 2016 and is 12 KB in size, are hereby incorporated by reference in their entireties.Model phage have been engineered using molecular biology techniques to deliver heterologous protein products to bacterial cells. For example, phage have been engineered to deliver enzymes to biofilms to digest the extracellular matrix and destroy the biofilm. (E.g., U.S. ...

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03-05-2018 дата публикации

Inactivation of Viruses

Номер: US20180119084A1
Принадлежит:

The invention discloses a bioreactor apparatus () for cultivation of cells comprising: a) a disposable bioreactor vessel () with one or more walls () defining an inner volume (), at least one port () in a wall, wherein the disposable bioreactor vessel is positioned in a rigid support structure (); and b) a heater (), capable of heating an amount of culture medium to a target temperature in the range of 55-95° C., while the amount of culture medium is being confined in or conveyed to the inner volume. 1. A bioreactor apparatus for cultivation of cells comprising:a) a disposable bioreactor vessel with one or more walls defining an inner volume, at least one port in said one or more walls, wherein said disposable bioreactor vessel is positioned in a rigid support structure; andb) a heater, capable of heating an amount of culture medium to a target temperature in the range of 55-95° C., said amount of culture medium being confined in or conveyed to said inner volume.2. The bioreactor apparatus of claim 1 , wherein said inner volume is at least 4 L claim 1 , such as at least 10 L claim 1 , at least 25 L claim 1 , at least 50 L claim 1 , at least 100 L claim 1 , at least 400 L claim 1 , 4-2500 L claim 1 , 10-2500 L claim 1 , 25-2500 L claim 1 , 25-500 L claim 1 , 50-2500 L claim 1 , 100-2500 L or 400-2500 L.3. The bioreactor apparatus of claim 1 , wherein said disposable bioreactor vessel is a flexible bag.4. The bioreactor apparatus of claim 1 , wherein said disposable bioreactor vessel comprises at least one agitator claim 1 , such as at least one magnetically driven impeller claim 1 , in said inner volume.5. The bioreactor apparatus of claim 1 , wherein said heater is capable of heating an amount of culture medium corresponding to at least 20% claim 1 , at least 50% or at least 60% of said inner volume to a target temperature in the range of 55-95° C.6. The bioreactor apparatus of any preceding claim of claim 1 , wherein said rigid support structure has one or more ...

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25-08-2022 дата публикации

Bacteriophage Hydrogel Compositions and Uses Thereof

Номер: US20220265739A1
Автор: HOSSEINIDOUST Zeinab
Принадлежит:

Described herein are hydrogel compositions comprising cross-linked bacteriophages. The hydrogels are typically bioactive, degradable, for example biodegradable, self-healing, fluorescent, for example autofluorescent, and/or birefringent. The hydrogels described herein may be used as therapeutics or diagnostics, as scaffolds for material synthesis, as catalysts, as membranes or filters, or as biosensor substrates, for example. 1. A hydrogel composition comprising cross-linked bacteriophages.2. The hydrogel composition of claim 1 , wherein the bacteriophages self-assemble into bundles.3. The hydrogel composition of claim 1 , wherein the bacteriophages comprise filamentous bacteriophages.4Escherichia coli. The hydrogel composition of claim 1 , wherein the bacteriophages comprise bacteriophages.5. The hydrogel composition of claim 1 , wherein the bacteriophages comprise f1 claim 1 , M13 claim 1 , or fd bacteriophages claim 1 , or combinations thereof.6. The hydrogel composition of claim 1 , wherein the bacteriophages comprise M13 bacteriophages.7. The hydrogel composition of claim 1 , wherein the bacteriophages comprise covalent crosslinks.8. The hydrogel composition of claim 1 , wherein the bacteriophages comprise non-covalent crosslinks.9. The hydrogel composition of claim 1 , wherein the bacteriophages are crosslinked with one or more crosslinkers comprising polyelectrolytes claim 1 , nanoparticles and/or nanocrystals.10. The hydrogel composition of claim 9 , wherein the one or more crosslinkers comprises glutaraldehyde.11. The hydrogel composition of claim 1 , wherein the hydrogel exhibits one or more of the following properties:bioactivity, for example antibacterial activity;degradability, such as biodegradability;self-healing, optionally in the presence of calcium ions and/or phosphate-buffered saline;fluorescent, such as autofluorescent; and/orbirefringence.12. The hydrogel composition of claim 1 , wherein the hydrogel comprises at least about 10PFU/mL ...

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04-05-2017 дата публикации

Methods and Systems for Rapid Detection of Microorganisms Using Infectious Agents

Номер: US20170121688A1
Принадлежит:

Disclosed herein are methods and systems for rapid detection of microorganisms in a sample. A genetically modified bacteriophage is also disclosed which comprises an indicator gene in the late gene region. The specificity of the bacteriophage, such as CBA120, allows detection of a specific microorganism, such as O157:H7, and an indicator signal may be amplified to optimize assay sensitivity. 1. A recombinant bacteriophage comprising an indicator gene inserted into a late gene region of the bacteriophage CBA120 genome.2E. coli. The recombinant bacteriophage of claim 1 , wherein the recombinant bacteriophage specifically infects O157:H7.3. The recombinant bacteriophage of claim 1 , wherein the indicator gene is codon-optimized and encodes a soluble protein product that generates an intrinsic signal or a soluble enzyme that generates signal upon reaction with substrate.4. The recombinant bacteriophage of claim 3 , further comprising an untranslated region upstream of the codon-optimized indicator gene claim 3 , wherein the untranslated region includes a bacteriophage late gene promoter and a ribosomal entry site.5. A method of preparing a recombinant indicator bacteriophage comprising:selecting a wild-type bacteriophage that specifically infects a target pathogenic bacterium;preparing a homologous recombination plasmid/vector comprising an indicator gene;transforming the homologous recombination plasmid/vector into target pathogenic bacteria;infecting the transformed target pathogenic bacteria with the selected wild-type bacteriophage, thereby allowing homologous recombination to occur between the plasmid/vector and the bacteriophage genome; andisolating a particular clone of recombinant bacteriophage.6. The method of claim 5 , wherein preparing a homologous recombination plasmid/vector comprises:determining the natural nucleotide sequence in the late region of the genome of the selected bacteriophage;annotating the genome and identifying the major capsid protein gene ...

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25-04-2019 дата публикации

A BACTERIOPHAGE STRAIN CAPABLE OF PRODUCING A LYTIC INFECTION IN THE ESCHERICHIA COLI ST131-O25B:H4 CLONE

Номер: US20190119652A1
Принадлежит:

The present invention relates to a bacteriophage strain capable of producing a lytic infection in the ST131-025b:H4 clone. The burden of STl31-025b:H4 clonal complex in human community and hospital-acquired infections is increasing worldwide, going along with a worrying and growing resistance to betalactams and fluoroquinolones. Bacteriophage LM33_P1 infects exclusively (100% specificity) 025b strains with 70% coverage on the two major antibiotic resistant pandemic clonal complexes STI31-025b:H4 and ST69-025b. The inventors evaluated the in vivo activity of bacteriophage LM33_P1 using three different extraintestinal virulence murine models and showed that it infects bacteria in several organs. In particular, the invention relates to a bacteriophage capable of producing a lytic infection in the ST131-025b:H4 clone comprising a polypeptide corresponding to the bacteriophage tail fiber protein and responsible for the attachment of the bacteriophage to the ST131-025b:H4 clone. 1Escherichia coliEscherichia coli. A bacteriophage capable of producing a lytic infection in the ST131-O25b:H4 clone comprising a polypeptide having an amino acid sequence having at least 80% of identity with the amino acid sequence of SEQ ID NO:1 wherein said polypeptide corresponds to the bacteriophage tail fiber protein and is responsible for the attachment of the bacteriophage to the ST131-O25b:H4 clone.2. The bacteriophage of which comprises a genomic sequence having at least 70% of identity with the genomic sequence of LM33-P1 represented by SEQ ID NO:2.3. The bacteriophage of which is the bacteriophage strain LM33-P1 deposited at the French National Collection of Microorganisms at the Institut Pasteur under Accession Number CNCM I-4964 or a variant thereof claim 1 , wherein the variant has the same lytic activity as said bacteriophage strain.4Escherichia coli. A method of treating an infection caused by an ST131-O25b:H4 clone in a patient in need thereof comprising administering to the ...

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25-04-2019 дата публикации

METHODS AND KITS FOR THE RAPID DETECTION OF THE ESCHERICHIA COLI O25B-ST131 CLONE

Номер: US20190120838A1
Принадлежит:

The present invention relates to methods and kits for the rapid detection of the O25b-ST131 clone. The inventors have isolated a podoviridae bacteriophage (LM33_P1) infecting the strain LM33 isolated from ventilator associated pneumonia and which belongs to clone STI3I-025b. By testing different strains of belonging to 129 others various distinct serotypes (including twelve O25a) the inventors found that bacteriophage LM33_P1 is able to infect exclusively O25b strains (none of non-O25b strains could be infected by LM33_P1). The inventors have determined that the specificity displayed by bacteriophage LM33_P1 to infect only 025b serotype strains is based on a very specific polypeptide (Gp17) used by LM33_P1 to attach the bacterial cell via LPS molecule. In particular, the present invention relates to a polypeptide comprising an amino acid sequence having at least 80% of identity with the amino acid sequence set forth in SEQ ID NO:1. 1. A polypeptide comprising an amino acid sequence having at least 80% of identity with the amino acid sequence set forth in SEQ ID NO:1.2. The polypeptide of which is fused to at least one heterologous polypeptide.3. The polypeptide of which is fused to an immunoglobulin domain such as a Fc portion.4. The polypeptide of which is fused to a fluorescent polypeptide.5. The polypeptide of which is fused to an enzyme.6. A nucleic acid molecule which encodes for the polypeptide of .7. The nucleic acid molecule of which is included in a vector.8. The polypeptide of which is conjugated with a detectable label.9. The polypeptide of wherein the label is a fluorescent label.10. The polypeptide of which is biotinylated.11. The polypeptide of which is conjugated to a latex particle claim 1 , a metal colloid particle claim 1 , or a carbon nanotube.12Escherichia coliEscherichia coliEscherichia coli. A method for detecting the presence of the O25b-ST131 clone in a sample comprising i) contacting the sample with the polypeptide of which is capable of ...

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03-06-2021 дата публикации

METHODS AND COMPOSITIONS FOR KILLING A TARGET BACTERIUM

Номер: US20210161150A1
Принадлежит:

Provided herein are methods and compositions for killing a target bacterium with a CRISPR-Cpf1 system. Also disclosed are engineered bacteriophages. 1. A method for killing a target bacterium comprising: (a) a first nucleic acid encoding a spacer sequence or a crRNA transcribed therefrom, wherein the spacer sequence is complimentary to a target nucleotide sequence from a target gene in the target bacterium; and', '(b) a second nucleic acid encoding a transcriptional activator for a CRISPR-Cpf1 system in a target bacterium;, 'introducing into a target bacterium a bacteriophage comprisingwherein the target bacterium is killed by lytic activity of the bacteriophage or activity of a CRISPR-Cpf1 system using the spacer sequence or the crRNA transcribed therefrom.2. The method of claim 1 , wherein the first nucleic acid sequence is a CRISPR array further comprising at least one repeat sequence.3. The method of any one of - claim 1 , wherein the transcriptional activator is endogenous to the target bacterium.4. The method of any one of - claim 1 , wherein the transcriptional activator is exogenous to the target bacterium.5. The method of any one of - claim 1 , wherein the transcriptional activator is regulated by Quorum Sensing (QS) signals.6. The method of any one of - claim 1 , wherein the transcriptional activator is a protein involved in sensing stress of a bacterium membrane.7. The method of any one of - claim 1 , wherein the transcriptional activator is a protein that stabilizes Cpf1.8. The method of claim any one of - claim 1 , wherein the transcriptional activator is a metabolic sensing protein.9. The method of claim 8 , wherein the metabolic sensing protein is a sigma factor.10. The method of any one of - claim 8 , wherein the transcriptional activator disrupts the activity of an inhibitory element.11. The method of claim 10 , wherein the inhibitory element is a transcriptional repressor.12. The method of claim 11 , wherein the transcriptional repressor is a ...

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03-06-2021 дата публикации

SEQUENCE SPECIFIC ANTIMICROBIALS

Номер: US20210162022A1
Принадлежит:

Provided are compositions and methods for selectively reducing the amount of antibiotic resistant and/or virulent bacteria in a mixed bacteria population, or for reducing any other type of unwanted bacteria in a mixed bacteria population. The compositions and methods involve targeting bacteria that are differentiated from other members of the population by at least one unique clustered regularly interspaced short palindromic repeats (CRISPR) targeted DNA sequence. The compositions and methods can be readily adapted to target any bacteria or any bacteria plasmid, or both. 1. (canceled)2Staphylococcus, Clostridium, Bacillus, Salmonella, Helicobacter pylori, Neisseria gonorrhoeae, Neisseria meningitidis,Escherichia coli,. A method of treating a bacterial infection in a subject , the method comprising selectively killing first bacteria comprised by the subject by cutting a target site comprised by the genomes of the first bacteria , wherein the cutting is carried out using a Cas nuclease that cleaves the target site , wherein the first bacteria are selected from the group consisting of and wherein the subject comprises a plurality of bacterial species that do not comprise the target site.3Staphylococcus aureus.. The method of claim 2 , wherein the first bacteria are4Staphylococcus aureus.. The method of claim 3 , wherein the first bacteria are a methicillin-resistant5. A method comprising:exposing a microbiota in a human patient to an antimicrobial agent to selectively kill cells of a first bacterial species in the microbiota,wherein selectively killing first bacteria comprised by the subject by cutting a target site comprised by the genomes of the first bacterial species,wherein the cutting is carried out using a Cas nuclease that cleaves the target site; andwherein the selective killing is carried out by avoiding killing second cells comprised by the microbiota, wherein the second cells are of a different strain or a different species from the first cells.6. The ...

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17-05-2018 дата публикации

PRODUCT FOR CLEANING, SANITIZING AND HYGIENIZATION

Номер: US20180134993A1
Принадлежит:

Product for cleaning, sanification and hygienization, comprising a base solution with sanificant and/or hygienizing action to which probiotic bacteria and bacteriophage elements are mixed; the probiotic bacteria being preferably of the and genera, while the bacteriophage elements comprise, as an alternative or in combination, bacteriophages of the Caudavirales, Microviridae, Leviviridae, Inoviridae, Tectiviridae, Corticoviridae families. 1. Product for cleaning , sanification and hygienization , comprising:a base solution with detergent, sanificant and hygienizing action containing at least a surfactant chosen among nonionic surfactants, cationic surfactants and amphoteric surfactants; probiotic bacteria spores mixed to such base solution; further comprising bacteriophage elements mixed to such base solution and having bactericidal action on predetermined undesired bacterial species occurring on contaminated surfaces, such bacteriophages elements, in cooperation with the probiotic bacteria spores being able to carry out a combined and synergistic action against harmful microorganisms.2. Product according to claim 1 , wherein the concentration of nonionic surfactants is between 0.001% and 30% claim 1 , the concentration of cationic surfactants is between 0.001% and 15% claim 1 , and the concentration of amphoteric surfactants is between 0.001% and 15%.3. Product according to claim 1 , wherein the concentration of probiotic bacteria spores mixed to the base solution is between 10and 10spores/ml claim 1 , preferably between 10and 10spores/ml.4. Product according to claim 1 , wherein the concentration of bacteriophage elements mixed to the base solution is between 10and 10PFU/ml claim 1 , preferably between 10and 10PFU/ml.5Bacillus. Product according to claim 1 , wherein the probiotic bacteria are of the genus.6Bacillus subtilis, Bacillus megateriumBacillus pumilis. Product according to claim 5 , wherein the probiotic bacteria are taken from the group consisting of the ...

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09-05-2019 дата публикации

PCSK9 VACCINE AND METHODS OF USING THE SAME

Номер: US20190134170A1
Принадлежит:

A vaccine construct comprising an antigenic PCSK9 peptide and an immunogenic carrier, and methods of using the same that are effective to lower blood cholesterol levels in a mammal and treat dyslipidemias and related disease states in a mammal without the frequency of administration required by passive immunity strategies. 120-. (canceled)22. The immunogen of claim 21 , wherein at least one amino acid is in the -isomeric form.23. The immunogen of claim 21 , wherein the immunogenic carrier is linked to the PCSK9 peptide through a succinimidyl-6-[β-maleimidopropionamido]hexanoate (SMPH) cross-linker molecule.24. A composition comprising the immunogen of .25. An immunogenic composition comprising the immunogen of and at least one adjuvant.27. The method according to claim 26 , wherein the dyslipidemia is selected from a group of hyperlipidemias consisting of type I claim 26 , type II claim 26 , type III claim 26 , type IV claim 26 , or type V hyperlipidemia claim 26 , secondary hypertriglyceridemia claim 26 , secondary hypercholesterolemia claim 26 , hypercholesterolemia claim 26 , familial hypercholesterolemia claim 26 , familial combined hyperlipidemia xanthomatosis claim 26 , and lecithin:cholesterol acetyltransferase deficiency.28. The method of claim 26 , wherein the immunogen is administered in combination with at least one additional therapeutic agent selected from the group consisting of a statin claim 26 , a bile acid sequestrant claim 26 , niacin claim 26 , a fibric acid derivative claim 26 , and a long chain alpha claim 26 , omego-dicarboxylic acid.30. The method of claim 29 , wherein the immunogen is administered in combination with at least one additional therapeutic agent selected from the group consisting of a statin claim 29 , a bile acid sequestrant claim 29 , niacin claim 29 , a fibric acid derivative claim 29 , and a long chain alpha claim 29 , omego-dicarboxylic acid.31. A nucleic acid encoding the immunogen of .32. An expression vector comprising ...

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26-05-2016 дата публикации

BACTERIOPHAGE THERAPY

Номер: US20160143965A1
Принадлежит:

The subject invention provides a pharmaceutical composition comprising: (i) at least one bacteriophage strain(s) capable of producing a lytic infection in an adherent-invasive strain; and (ii) a pharmaceutically acceptable carrier; for the treatment of inflammatory bowel disease. The subject invention further provides a method of treating inflammatory bowel disease comprising administering to a subject in need thereof at least one bacteriophage strain capable of producing a lytic infection in an adherent-invasive strain thereby treating the subject. The subject invention also provides new bacteriophage strains. 1. A pharmaceutical composition comprising:{'i': 'Escherichia coli', '(i) at least one bacteriophage strain(s) capable of producing a lytic infection in an adherent-invasive strain; and'}(ii) a pharmaceutically acceptable carrier;for use in the treatment of inflammatory bowel disease.2Escherichia coli. A composition according to wherein the adherent-invasive strain is present in one or more of the intestinal parts (small and large) of the subject.3Escherichia coli. A composition according to wherein the adherent-invasive strain is LF82 claim 1 , 07081 claim 1 , 07082 claim 1 , 07076 or 06075.4. A composition according to any one of to wherein the inflammatory bowel disease is Crohn's disease.5. A composition according to any one of to wherein the inflammatory bowel disease is ulcerative colitis.6. A composition according to any one of to wherein the inflammatory bowel disease is recurrence of ileal lesions after surgery claim 1 , for example surgery to remove at least a part of the small intestine in CD patients.7. A composition according to any one of to wherein the composition comprises the bacteriophage strain P1 deposited with the French National Collection of Microorganisms at the Institut Pasteur under Accession Number CNCM I-4694 or a variant thereof claim 1 , wherein the variant has the same lytic activity claim 1 , preferably the same lytic activity ...

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16-05-2019 дата публикации

Bacteriophage compositions and uses thereof

Номер: US20190142881A1
Принадлежит: YALE UNIVERSITY

The present invention includes compositions and methods of bacteriophage to increase antibiotic sensitivity in bacteria. In one aspect, the invention includes a method of increasing antibiotic sensitivity in multi-drug resistant (MDR) bacteria. Another aspect includes a pharmaceutical composition comprising a lytic bacteriophage. Yet another aspect includes a method of treating a multi-drug resistant bacterial infection in a subject. Yet another aspect includes a method of disrupting a pathogenic bacteria associated with a biofilm and compositions for use thereof.

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16-05-2019 дата публикации

Microbial production of pure single stranded nucleic acids

Номер: US20190142882A1
Принадлежит: Massachusetts Institute of Technology

Methods and compositions for bacterial production of pure single-stranded DNA (ssDNA) composed of custom sequence and size have been developed. The methods enable scalability and bio-orthogonality in applications of scaffolded DNA origami, offering one-step purification of large quantities of pure ssDNA amendable for immediate folding of DNA nanoparticles. The methods produce pure ssDNA directly from bacteria. In some embodiments the E. coli helper strain M13cp combined with a phagemid carrying only an f1 -origin allows for, without the need for additional purification from contaminating dsDNA. This system is useful for generalized circular ssDNA synthesis, and here is applied to the assembly of DNA nanoparticles folded both in vitro and direct from phage.

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07-05-2020 дата публикации

Di-enzymatic chimeric endolysin

Номер: US20200140837A1
Принадлежит: US Department of Commerce

A di-enzymatic chimeric endolysin includes a primary enzymatic active domain including a primary protein sequence and that cleaves a glycosidic, peptide, or amide bond; a secondary enzymatic active domain disposed at a C-terminus end of the di-enzymatic chimeric endolysin and including a secondary protein sequence that, in combination with the primary enzymatic active domain, synergistically cleaves glycosidic, peptide, or amide bonds in a peptidoglycan; a cell wall binding domain including a recognition sequence that is sequentially interposed between the primary protein sequence and the secondary protein sequence and that binds to a cell wall; and a tertiary structure such that the primary enzymatic active domain faces and opposes the secondary enzymatic active domain in the di-enzymatic chimeric endolysin for synergistic cleavage of the peptidoglycan.

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07-05-2020 дата публикации

Methods and Systems for Rapid Detection of Microorganisms Using Infectious Agents

Номер: US20200140919A1

Disclosed herein are methods and systems for rapid detection of microorganisms in a sample, without culturing for enrichment of the microorganism. A modified bacteriophage is also disclosed which comprises a non-native indicator gene in the late gene region. The indicator product is not a fusion protein. The specificity of infectious agents allows a specific microorganism to be targeted, and an indicator signal may be amplified to optimize assay sensitivity. 132-. (canceled)33. A method for detecting a bacterium of interest in a sample ,the method comprising the steps of:infecting the at least one bacterium with a plurality of a parental bacteriophage genetically engineered to express a soluble protein during replication, wherein the soluble protein is luciferase protein;incubating the at least one infected bacterium until it is lysed to release progeny bacteriophage present in the bacterium; anddetecting the soluble protein expressed during replication of the progeny bacteriophage,wherein detection of the soluble protein indicates that the bacterium is present in the sample, andwherein the method detects as little as a single bacterium in the sample.34. The method of claim 33 , wherein expression of the soluble protein is driven by a viral capsid promoter and the soluble protein is not a fusion protein and is not incorporated into the bacteriophage structure.35. The method of claim 33 , wherein the method is performed without culturing for enrichment of bacteria in the sample.36. The method of claim 33 , wherein the parental bacteriophage are not separated from the progeny bacteriophage before detecting.37. The method of claim 33 , wherein the progeny bacteriophage comprise an indicator moiety.38. The method of claim 37 , wherein the indicator moiety comprises soluble luciferase protein.39. The method of claim 33 , wherein the phage is a T4 phage.40E. coli.. The method of claim 33 , wherein the bacterium is41. The method of claim 33 , wherein the plasmid further ...

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09-06-2016 дата публикации

THERAPEUTIC PHAGES AND METHODS FOR DELIVERY OF NUCLEIC ACIDS FOR THERAPEUTIC USES

Номер: US20160160186A1
Принадлежит:

Compositions for a phage particle are disclosed. The phage particle is non-replicating and includes at least one heterologous nucleic acid sequence that is capable of being expressed in a target bacteria. The expressed heterologous nucleic acid sequence is non-lethal to the target bacteria. 1. A method for delivering a nucleic acid sequence comprising the steps of:providing, in vivo, a composition derived from a phage including at least one nucleic acid sequence and a bacterial origin of replication which are packaged into one or more structural proteins of the phage and a receptor binding protein where the composition is devoid of one or more functional phage replication genes rendering it incapable of independent production of phage progeny;attaching the composition to a target bacteria in a microbiome via the receptor binding protein; andexpressing the nucleic acid sequence in the target bacteria where the expression of the nucleic acid sequence and the expressed nucleic acid sequence are non-lethal to the target bacteria and the expressed nucleic acid sequence produces a therapeutic effect.2. (canceled)3. The method according to claim 1 , wherein the nucleic acid sequence is DNA and/or RNA.4. The method according to claim 1 , wherein the nucleic acid sequence encodes regulatory sequences for in vivo expression and targeting of the therapeutic effect.5. (canceled)6. (canceled)7. The method according to claim 3 , wherein the RNA is a trans-kingdom RNAi for expression in a microbiome and delivery claim 3 , in vivo claim 3 , to another cell.840-. (canceled)41. The method according to claim 1 , wherein the microbiome is associated with a living organism.42. The method according to claim 41 , wherein the expressing of the nucleic acid sequence occurs at sites of greater significance for a particular issue that can be treated by the therapeutic effect.43. The method according to claim 1 , wherein the nucleic acid sequence also encodes at least one element capable of ...

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22-09-2022 дата публикации

MODULAR PHAGE VECTOR PLATFORM FOR SONODYNAMIC THERAPY

Номер: US20220296710A1

The present invention relates to a phage or a composition that comprises it, wherein said phage expresses at least one specific recognition element and is furthermore conjugated with at least 300 molecules of a sonosensitiser. The invention further relates to the use of said phage in a sonodynamic therapy. 1. A phage expressing at least one specific recognition element that and is conjugated with at least 300 molecules of a sonosensitiser.2. The phage according to claim 1 , wherein the sonosensitiser is selected from: Bacteriochlorin claim 1 , Phthalocyanines claim 1 , Pheophorbide A and B claim 1 , Bacteriopheophorbide claim 1 , Naphthalocyanine claim 1 , BODIPY stains claim 1 , Anthracycline claim 1 , Tetracycline claim 1 , Fluoroquinolones claim 1 , Phenothiazine claim 1 , Perylene claim 1 , Perylenequinone claim 1 , Curcumin claim 1 , Quinones claim 1 , Anthraquinones claim 1 , Fullerenes claim 1 , Endohedral Metallofullerenes claim 1 , Acridines claim 1 , Isoquinole alkaloids claim 1 , Xanthenes claim 1 , Porphyrins claim 1 , Chlorins and Cyanine.3. The phage according to claim 1 , wherein the sonosensitiser is selected from: a xanthen claim 1 , a porfirin claim 1 , a chlorin claim 1 , a cyanine and combinations thereof.4. The phage according to claim 3 , wherein the xanthen is selected from rose bengal claim 3 , eosin claim 3 , erythrosin B claim 3 , fluorescein and rhodamine; the porphyirin is selected from protoporphyirin IX claim 3 , hematoporphyirin claim 3 , porfimer sodium and ATX-70; the chlorin is selected from chlorin e6 claim 3 , temoporfin and verteporfin; the cyanine is selected from cyanine IR-806 claim 3 , indocyanine green and cyanine IR-780 claim 3 , and combinations thereof.5. The phage according to claim 1 , wherein said phage is conjugated with at least 400 sonosensitiser molecules.6. The phage according to claim 1 , wherein the phage is selected from the M13 phage claim 1 , fd phage claim 1 , Ff phage claim 1 , T4 and MS2 phage.7. The phage ...

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14-05-2020 дата публикации

DUAL ANTHRAX-PLAGUE VACCINES THAT CAN PROTECT AGAINST TWO TIER-1 BIOTERROR PATHOGENS, BACILLUS ANTHRACIS AND YERSINIA PESTIS

Номер: US20200147207A1
Автор: Rao Venigalla B.
Принадлежит:

Bivalent immunogenic compositions against anthrax and plague are disclosed herein. One bivalent immunogenic composition comprises a triple fusion protein containing three antigens, F1 and V from and PA antigen from fused in-frame and retaining structural and functional integrity of all three antigens. Another bivalent immunogenic composition comprises bacteriophage nanoparticles arrayed with these three antigens on the capsid surface of the bacteriophage nanoparticles. These bivalent immunogenic compositions are able to elicit robust immune response in a subject administered said the bivalent immunogenic compositions and provide protection to the subject against sequential or simultaneous challenge with both anthrax and plague pathogens. 1. An immunogenic composition comprising a triple fusion protein , [{'i': 'Yersinia pestis,', 'a mutated F1 antigen from'}, {'i': 'Yersinia pestis', 'a V antigen from , and'}, {'i': 'B. anthracis;', 'a protective antigen (PA) from'}], 'wherein the triple fusion protein compriseswherein the mutated F1 antigen, the V antigen, and the PA are fused in-frame;wherein the triple fusion protein has an immunogenicity of the mutated F1 antigen, an immunogenicity of the V antigen, and an immunogenicity of the PA.2. The immunogenic composition of claim 1 , wherein the mutated F1 antigen is fused in-frame to the N-terminus of the V antigen via a first linker claim 1 , and wherein the V antigen is fused in-frame to the N-terminus of PA via a second linker.3. The immunogenic composition of claim 1 , wherein the mutated F1 antigen is modified from a native F1 antigen by deleting N-terminal β-strand residues 1-14 of native F1 antigen claim 1 , transplanting the N-terminal β-strand residues 1-14 of native F1 antigen to C-terminus claim 1 , and duplicating residues 15-21 of native F1 antigen at the C-terminus.4. The immunogenic composition of claim 1 , wherein the mutated F1 antigen comprises a sequence set forth in SEQ ID NO: 1.5. The immunogenic ...

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07-06-2018 дата публикации

Synthetic bacteriophages and bacteriophage compositions

Номер: US20180155721A1
Принадлежит: Massachusetts Institute of Technology

Disclosed herein are novel synthetic bacteriophages and bacteriophage compositions, methods of production thereof, and therapeutic uses thereof.

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07-06-2018 дата публикации

METHODS AND COMPOSITIONS FOR EFFICIENT DELIVERY OF NUCLEIC ACIDS AND RNA-BASED ANTIMICROBIALS

Номер: US20180155729A1
Принадлежит:

The invention relates to the methods for modifying the methylation pattern of bacteriophage DNA and phagemid DNA and to methods for selective killing of bacteria using lysogenic bacteriophages comprising bacteriophage DNA or phagemid DNA comprising components of an engineered CRISPR-Cas system. 1. A method of modifying the methylation pattern of a bacteriophage DNA or phagemid DNA , comprising: (1) disrupting the activity of at least one enzyme of an endogenous restriction modification system (R-M system) of a production host bacterium, thereby producing a modified production host bacterium having the activity of at least one enzyme of the endogenous R-M system disrupted, and/or', '(2) introducing into a production host bacterium a polynucleotide encoding at least one heterologous methyltransferase, thereby producing a modified production host bacterium expressing the heterologous methyltransferase;, 'altering methylating activity of a production host bacterium, comprising'}infecting the modified production host bacterium having an altered methylating activity with a bacteriophage particle comprising bacteriophage DNA or phagemid DNA, thereby methylating said bacteriophage DNA or phagemid DNA; andproducing a bacteriophage particle comprising bacteriophage DNA or phagemid DNA having a modified methylation pattern.2. A method of modifying the methylation pattern of a bacteriophage DNA or phagemid DNA , comprising:infecting a production host bacterium with a bacteriophage particle comprising bacteriophage DNA or phagemid DNA, wherein the production host bacterium has altered methylating activity via disruption of at least one enzyme of an endogenous R-M system and/or expression of at least one heterologous methyltransferase, thereby methylating said bacteriophage DNA or phagemid DNA; andproducing a bacteriophage particle comprising bacteriophage DNA or phagemid DNA having a modified methylation pattern.3. The method of any one of to , wherein two or more enzymes of the ...

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04-09-2014 дата публикации

Dimeric bacteriophage lysins

Номер: US20140248256A1
Принадлежит: ROCKEFELLER UNIVERSITY

The present invention provides isolated dimeric Streptococcus -specific phage lysins having two Streptococcus -specific phage lysin monomers covalently linked to each other, and having killing activity against one or more Streptococcus bacteria. Also provided for are pharmaceutical compositions of dimeric lysins and their use in therapeutic treatment or alleviation of infections or bacterial colonizations. The dimeric lysins may also be used to decontaminate porous and non-porous surfaces or devices.

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29-09-2022 дата публикации

METHODS AND COMPOSITIONS FOR MICROBIAL DELIVERY OF DOUBLE STRANDED RNA

Номер: US20220304315A1
Принадлежит: RNAISSANCE AG LLC

Methods and materials for improved delivery of dsRNA are presented. In particular, methods for controlling an insect pest by stably delivering large quantities of dsRNA to the insect pest are provided. Compositions comprising a bacterium containing a large quantity of dsRNA targeting an insect gene in which the dsRNA exhibits increased stability and activity are also provided. 146-. (canceled)47. A method for controlling an insect pest comprising contacting the insect pest with a composition comprising a microorganism comprising (i) a promoter operably linked to a DNA sequence encoding a dsRNA molecule that specifically inhibits expression of a target gene in an insect pest and (ii) a promoter operably linked to a DNA sequence comprising a coat protein gene encoding a capsid protein or a portion thereof.48. The method according to claim 47 , wherein the capsid protein is encoded by a leviviridae coat protein gene.49. The method according to claim 47 , wherein the capsid protein is encoded by the coat protein gene of bacteriophage MS2 or bacteriophage Q13.50. The method according to claim 47 , wherein the DNA sequence encoding the dsRNA and the coat protein gene encoding the capsid protein are present on one plasmid or extrachromosomal element within the microorganism.51. The method according to claim 50 , wherein the plasmid or extrachromosomal element is pAPSE10180 (SEQ ID NO: 1) claim 50 , pAPSE10269 (SEQ ID NO: 8) claim 50 , pAPSE10216 (SEQ ID NO: 10) claim 50 , pAPSE10219 (SEQ ID NO: 12) claim 50 , pAPSE10279 (SEQ ID NO: 14) claim 50 , pAPSE10270 (SEQ ID NO: 16) claim 50 , pAPSE10271 (SEQ ID NO: 17) claim 50 , pAPSE10272 (SEQ ID NO: 18) pAPSE10292 (SEQ ID NO: 19) claim 50 , pAPSE10291 (SEQ ID NO: 20) claim 50 , pAPSE10359 (SEQ ID NO: 25) claim 50 , pAPSE10372 (SEQ ID NO: 27) claim 50 , pAPSE10429 (SEQ ID NO: 29) claim 50 , pAPSE10430 (SEQ ID NO: 31) claim 50 , pAPSE10431 (SEQ ID NO: 32) claim 50 , pAPSE10432 (SEQ ID NO: 33) claim 50 , pAPSE10434 (SEQ ID NO: 35) ...

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30-05-2019 дата публикации

DNA, METHODS ETC

Номер: US20190160120A1
Автор: HAABER Jakob Krause
Принадлежит: SNIPR Biome ApS

The invention relates to the production of phage and transduction particles using DNAs (eg, plasmids and helper phage, mobile genetic elements (MGEs) or plasmids with chromosomally integrated helper phage genes), as well as the phage, helper phage, kits, compositions and methods involving these. 1119-. (canceled)120. An antibacterial composition comprising a plurality of non self-replicative transduction particles comprising a nucleic acid encoding an antibacterial agent or component thereof , wherein the antibacterial agent is toxic to target bacterial cells , wherein the particles are capable of transducing into the target bacterial cells the nucleic acid encoding the antibacterial agent or component thereof for expression of the antibacterial agent or component in the target bacterial cells; a) the antibacterial agent comprises a guided nuclease system;', 'b) the particles comprise one, more or all of the tail proteins, portal protein and tail fiber proteins of a first phage and capsid proteins of the first phage;', 'c) the nucleic acid comprises an origin of replication (ori) operable in a bacterial host cell for replication of the nucleic acid encoding the antibacterial agent or component thereof, wherein the first phage is capable of infecting cells of the same species or strain as the bacterial host cell;', 'd) the nucleic acid comprises a packaging signal comprising a pac, cos or a homologue thereof that is operable with the first phage to package the nucleic acid in non self-replicative transduction particles;', 'e) the particles are devoid of all phage terminase genes; and', 'f) the particles are devoid of all phage structural protein genes., 'wherein'}121. The antibacterial composition of claim 120 , wherein the particles are devoid of all phage genes.122. The antibacterial composition of claim 120 , wherein the nucleic acid is comprised by a shuttle vector that can be replicated in first bacteria claim 120 , wherein the shuttle vector can further be ...

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29-09-2022 дата публикации

IMPROVED METHODS AND COMPOSITIONS FOR INCREASED DOUBLE STRANDED RNA PRODUCTION

Номер: US20220307038A1
Автор: Kumar Anil
Принадлежит: RNAISSANCE AG LLC

The invention provides methods and compositions for improved production of large quantities of unencapsidated doublestrand RNA (dsRNA) in vivo. The disclosed methods and compositions, comprising co-expression of genes encoding orotate phospori-bosyl transferase, bacteriophage coat protein and dsRNA produce a significant improvement over current in vivo methods of producing unencapsidated dsRNA. 15-.(canceled)6. A modified bacterial cell for producing dsRNA in vivo , the modified bacterial cell comprising:a. a genetic modification for increasing expression of a pyrE gene;b. a nucleic acid construct comprising a nucleic acid sequence encoding a double-stranded RNA (dsRNA) operably linked to an expression control sequence; andc. a nucleic acid construct comprising a nucleic acid sequence encoding a capsid protein operably linked to an expression control sequence.7. The modified bacterial cell of claim 6 , wherein the dsRNA is selected from the group consisting of siRNA claim 6 , shRNA claim 6 , sshRNA claim 6 , and miRNA.8. The modified bacterial cell of claim 6 , wherein the capsid protein is a leviviridae coat protein gene encoding a capsid protein.9. The modified bacterial cell of claim 6 , wherein the capsid protein is a capsid protein of bacteriophage MS2 or N-terminal 41 claim 6 , 35 claim 6 , 25 claim 6 , 21 or 12 amino acids of the MS2 capsid protein.10. The modified bacterial cell of claim 6 , wherein the capsid protein is a capsid protein of bacteriophage Qβ or N-terminal 41 claim 6 , 35 claim 6 , 25 claim 6 , 21 or 12 amino acids of the Qβ capsid protein.11E. coli. The modified bacterial cell of claim 6 , wherein the bacterial cell is an K-12 strain comprising a frameshift mutation in a rph gene.12E. coliE. coli. The modified bacterial cell of claim 11 , wherein the K-12 strain comprising a frameshift mutation in the rph gene comprises orotate phosphoribosyltransferase (ORPTase) with a specific activity of about 5-20 units and wherein the K-12 strain ...

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01-07-2021 дата публикации

Bacterial delivery vehicles for in vivo delivery of a dna payload

Номер: US20210196828A1
Принадлежит: Eligo Bioscience

The present disclosure relates generally to bacterial delivery vehicles and their use in efficient transfer of a desired payload into a target bacterial cell of the microbiota of a subject. More specifically, the present disclosure relates to bacterial delivery vehicles with desired host ranges that can be used to efficiently transfer the desired payload in vivo to one or more target bacterial cells of the microbiota of a subject.

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23-06-2016 дата публикации

COMPOSITIONS AND METHODS USING CAPSIDS RESISTANT TO HYDROLASES

Номер: US20160177299A1
Принадлежит: APSE LLC

Novel processes and compositions are described which use viral capsid proteins resistant to hydrolases to prepare virus-like particles to enclose and subsequently isolate and purify target cargo molecules of interest including nucleic acids such as siRNAs and shRNAs, miRNAs, messenger RNAs, small peptides and bioactive molecules. 1. A virus-like particle (VLP) comprising a protease resistant capsid enclosing at least one heterologous cargo molecule , the cargo molecule further comprising a capsid specific packing sequence.2. A VLP according to claim 1 , wherein the heterologous cargo molecule comprises an oligoribonucleotide.3. A nucleic acid encoding the oligoribonucleotide of .433-. (canceled)34. A method for producing double stranded RNA comprising; (a) mixing equal amounts of a first VLP of and a second VLP of ; (b) isolating the heterologous cargo molecules thereof; (c) annealing the heterologous cargo molecules to form a double stranded RNA molecule; (d) isolating the double stranded RNA molecule.35. A method for producing siRNA claim 34 , shRNA claim 34 , sshRNA claim 34 , lshRNA and miRNA comprising transforming a host cell with the double stranded RNA of .36. The nucleic acid of claim 3 , comprising one or more complementary regions claim 3 , each of said complementary regions comprising;(a) a sense strand siRNA, immediately followed by(b) RNA capable of forming a loop, immediately followed by(c) an antisense strand siRNA complementary to the sense strand siRNA are contiguously arrayed.37. The nucleic acid of claim 36 , wherein the complementary regions are linked by one or more ribozymes.39. The nucleic acid of claim 38 , wherein multiple catenated sense strand siRNAs are linked by 1 to 3 non-complementary nucleotides to form bulged RNA.41. The nucleic acid of claim 40 , wherein the RNA sequence for host cell RNA processing is CRISPER.4210. The nucleic acid of claim claim 40 , wherein the RNA sequence for host cell RNA processing is DICER.43. The nucleic ...

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06-06-2019 дата публикации

BACTERIOPHAGE FOR TREATING STAPHYLOCOCCUS INFECTIONS

Номер: US20190167736A1
Принадлежит:

The present invention relates to GRCS bacteriophages, as well as to methods and compositions for the treatment of prosthetic joint infection. Particularly, the present invention provides bacteriophages specific against from prosthetic joint infections. 1Staphylococcus aureus. A method for treating prosthetic joint infection involving , comprising administering to the infected area and/or surface of the prosthetic a GRCS bacteriophage or a Podoviridae bacteriophage having a minor tail protein encoded by GRCS bacteriophage gene 18505614 , or a functional derivative thereof.2. The method of claim 1 , wherein the functional derivative comprises an amino acid sequence having at least 70% identity with the minor tail protein encoded by GRCS bacteriophage gene 18505614.3Staphylococcus aureus.. The method of claim 1 , wherein the minor tail protein or the functional derivative thereof recognizes a surface determinant on4. The method of claim 1 , wherein the prosthetic joint infection is a mixed infection comprising one or more additional microbial strains.5. The method of claim 4 , wherein the additional microbial strain is Gram-positive or Gram-negative.6. (canceled)7Staphylococcus aureus.. The method of claim 1 , wherein the bacteriophage eliminates the8. (canceled)9. The method of claim 1 , wherein the bacteriophage comprises a nucleic acid encoding a biofilm-degrading enzyme.10. (canceled)11. The method of claim 1 , wherein the bacteriophage comprises a nucleic acid encoding at least one antimicrobial polypeptide.1218.-. (canceled)19. The method of claim 1 , wherein the bacteriophage comprises a nucleic acid encoding at least one agent that inhibits an antibiotic resistance gene and/or a cell survival repair gene.20. The method of claim 1 , wherein the bacteriophage comprises a nucleic acid encoding at least one repressor of a SOS response gene and/or bacterial defense gene.2123.-. (canceled)24. The method of claim 1 , wherein the bacteriophage comprises a nucleic acid ...

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21-06-2018 дата публикации

Processes for packaging oligonucleotides into virus-like particles of rna bacteriophages

Номер: US20180171358A1
Принадлежит: KUROS BIOSCIENCES AG

The invention provides processes for the producing compositions comprising (i) a virus-like particle, wherein said virus-like particle is a virus-like particle of an RNA bacteriophage, and (ii) an oligonucleotide, wherein said oligonucleotide is packaged into said virus-like particle. The invention further provides processes for producing nucleotide compositions comprising oligonucleotides suitable to be used in the processes mentioned before. The invention further provides nucleotide compositions obtainable by the processes of the invention and uses thereof. The invention further provides compositions comprising (i) a virus-like particle, wherein said virus-like particle is a virus-like particle of an RNA bacteriophage, and (ii) an oligonucleotide, wherein said oligonucleotide is packaged into said virus-like particle, wherein said compositions are obtainable by the processes of the invention and wherein said compositions preferably comprises a purity of at least 98%, most preferably of at least 99%.

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18-09-2014 дата публикации

Therapeutic cancer vaccine targeted to haah (aspartyl-[asparaginyl]-beta-hydroxylase)

Номер: US20140271691A1
Принадлежит: Panacea Pharmaceuticals Inc

The present invention encompasses a cancer vaccine therapy targeting Aspartyl-[Asparaginyl]-β-hydroxylase (HAAH). The present invention contemplate bacteriophage expressing HAAH peptide fragments and methods for using said bacteriophage in methods of treating cancer.

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04-06-2020 дата публикации

Mechanical Method Of Maintaining Narrow Residence Time Distributions In Continuous Flow Systems

Номер: US20200172568A1
Принадлежит:

Methods of maintaining narrow residence time distributions in continuous flow systems, particularly applicable to virus inactivation such as during a protein purification process. Fluid sample is introduced into an axial flow channel and caused to flow therein in discrete packets or zones to minimize residence time distribution and axial dispersion. Embodiments described herein obviate or minimize the need for using large tanks or reservoirs for performing virus inactivation during a protein purification process; reduce the overall time required for virus inactivation, and/or reduce the overall physical space required to perform the virus inactivation operation during a protein purification process, which in turn reduces the overall footprint for the purification process. 1. A method for maintaining a narrow residence time distribution of a fluid sample flowing in a fluid channel having an axial length , comprising causing said fluid sample to flow in discrete packets along said axial length within said fluid channel.2. The method of claim 1 , wherein said fluid sample is caused to flow in discrete packets by applying compressive force to said fluid channel.3. The method of claim 1 , wherein said fluid sample has a nominal residence time in said fluid channel of one to two minutes.4. The method of claim 1 , wherein said fluid sample has a nominal residence time in said fluid channel of two to four minutes.5. The method of claim 1 , wherein said fluid sample has a nominal residence time in said fluid channel of four to six minutes.6. The method of claim 1 , wherein said fluid sample has a nominal residence time in said fluid channel of six to eight minutes.7. The method of claim 1 , wherein said fluid sample has a nominal residence time in said fluid channel of eight to ten minutes.8. The method of claim 1 , wherein said fluid sample has a nominal residence time in said fluid channel of ten to fifteen minutes.9. The method of claim 1 , wherein said fluid sample has a ...

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15-07-2021 дата публикации

DELIVERY OF THERAPEUTIC RNAS VIA ARRDC1-MEDIATED MICROVESICLES

Номер: US20210213139A1
Автор: Lu Quan

Methods, systems, compositions and strategies for the delivery of RNA into cells in vivo, ex vivo, or in vitro via ARMMs are provided. In some aspects, ARMMs containing fusion proteins of ARRDC1 fused to an RNA binding protein or an RNA binding protein fused to a WW domain are provided. In some aspects, ARMMs containing binding RNAs associated with cargo RNAs are provided. In other aspects, cargo RNAs associated with a binding RNA, such as a TAR element, are loaded into ARMMs via ARRDC1 fusion proteins containing an RNA binding protein, such as trans-activator of transcription (Tat) protein. 1. An arrestin domain-containing protein 1 (ARRDC1)-mediated microvesicle (ARMM) , comprising:an ARRDC1 protein or variant thereof, wherein the ARRDC1 protein, or variant thereof, is associated with an RNA binding protein, or variant thereof, anda binding RNA, wherein the binding RNA is associated with the RNA binding protein.2. An arrestin domain-containing protein 1 (ARRDC1)-mediated microvesicle (ARMM) , comprising:an ARRDC1 protein or variant thereof, andan RNA binding protein fused to at least one WW domain or variant thereof, anda binding RNA, wherein the binding RNA is associated with the RNA binding protein.3. The microvesicle of claim 2 , wherein the RNA binding protein comprises two claim 2 , three claim 2 , four or five WW domains.4. The microvesicle of or claim 2 , wherein at least one WW domain is derived from a WW domain of the ubiquitin ligase WWP1 claim 2 , WWP2 claim 2 , Nedd4-1 claim 2 , Nedd4-2 claim 2 , Smurf1 claim 2 , Smurf2 claim 2 , ITCH claim 2 , NEDL1 or NEDL2.5. The microvesicle of any of - claim 2 , wherein the ARRDC1 protein or variant thereof comprises at least one PPXY (SEQ ID NO: 2) motif.6. The microvesicle of any one of - claim 2 , further comprising a TSG101 protein or variant thereof.7. The microvesicle of claim 6 , wherein the TSG101 protein variant comprises a TSG101 UEV domain.8. The microvesicle of any one of - claim 6 , wherein the ...

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07-07-2016 дата публикации

COMPOSITIONS AND METHODS FOR INHIBITING GENE EXPRESSIONS

Номер: US20160194613A1
Принадлежит:

A combined packing and assembly method that efficiently packs ribonucleic acid (RNA) into virus like particles (VLPs) has been developed. The VLPs can spontaneously assemble and load RNA in vivo, efficiently packaging specifically designed RNAs at high densities and with high purity. In some embodiments the RNA is capable of interference activity, or is a precursor of a RNA capable of causing interference activity. Compositions and methods for the efficient expression, production and purification of VLP-RNAs are provided. VLP-RNAs can be used for the storage of RNA for long periods, and provide the ability to deliver RNA in stable form that is readily taken up by cells. 1. A virus like particle (VLP) containing ribonucleic acid (RNA) comprisinga) a virus like particle formed from coat proteins of a bacteriophage; andb) RNA comprising a capsid binding tag; andwherein the coat proteins of the bacteriophage self-assemble to encapsidate three of the RNAs per VLP.2. The VLP containing RNA of wherein the RNA is processed in vivo into short interfering RNAs (siRNAs).3. The VLP containing RNA of wherein the bacteriophage coat protein is the bacteriophage q beta coat protein.4. The VLP containing RNA of wherein the VLP stabilizes the RNA against chemical claim 1 , photochemical and enzymatic degradation processes.5. The VLP containing RNA of wherein the RNA comprises one or more selected from the group consisting of thermal-stable tetraloops claim 1 , G-quartets claim 1 , and triple strands.6. The VLP containing RNA of wherein the RNA is at least 180 nucleotides in length.7. The VLP containing RNA of wherein the encodes the RNA is inhibitory RNA specific for cellulase of a cellulose dependent insect.8Reticulitermes flavipes.. The VLP containing RNA of wherein the cellulose dependent insect is the eastern termite9. The VLP containing RNA of wherein the RNA is inhibitory RNA specific tumor-specific transcription factors.10. The VLP containing RNA of wherein the RNA is ...

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07-07-2016 дата публикации

Targeting non-coding rna for rna interference

Номер: US20160194632A1
Принадлежит: Georgia Tech Research Corp

A broad and extensive new category of targets for ribonucleic acids (RNAs) with interference activity (iRNAs), exclusive of the traditional messenger RNA (mRNA) targets have been discovered. iRNAs can be used to manipulate biological processes that do not explicitly involve mRNA and can be directed at non-coding RNAs, such as ribosomal RNAs (rRNAs) and transfer RNAs (tRNAs). iRNA sequences targeted at ribosomal rRNAs and tRNAs have been designed and tested. iRNA that targets a non-coding RNA is called non-coding interfering RNA (nciRNA). nciRNAs cause degradation of non-coding RNAs in vivo, and are highly active in biological assays. nciRNAs can be used as programmed toxins for specific targeting of eukaryotic pathogens and for protection of plants and structures from insects and weeds.

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06-07-2017 дата публикации

PCSK9 VACCINE AND METHODS OF USING THE SAME

Номер: US20170189503A1
Принадлежит:

A vaccine construct comprising an antigenic PCSK9 peptide and an immunogenic carrier, and methods of using the same that are effective to lower blood cholesterol levels in a mammal and treat dyslipidemias and related disease states in a mammal without the frequency of administration required by passive immunity strategies. 1. An immunogen comprising:an antigenic PCSK9 peptide linked to a bacteriophage virus-like particle (VLP) Qbeta immunogenic carrier, the antigenic PCSK9 peptide selected from the group consisting of the amino acid sequence NVPEEDGTRFHRQASKC (SEQ ID NO:3) and the amino acid sequence CKSAQRHFRTGDEEPVN (SEQ ID NO:4).2. The immunogen of claim 1 , wherein at least one amino acid is in the -isomeric form.3. The immunogen of claim 1 , wherein the immunogenic carrier is linked to the PCSK9 peptide through a succinimidyl-6[β-maleimidopropionamido]hexanoate (SMPH) cross-linker molecule.4. A composition comprising the immunogen of .5. An immunogenic composition comprising the immunogen of and at least one adjuvant.6. A method of preventing claim 1 , alleviating claim 1 , or treating a dyslipidemia in an individual claim 1 , the method comprising administering a therapeutically effective amount of an immunogen to the individual claim 1 , the immunogen comprising:an antigenic PCSK9 peptide linked to a bacteriophage virus-like particle (VLP) Qbeta immunogenic carrier, the antigenic PCSK9 peptide selected from the group consisting of the amino acid sequence NVPEEDGTRFHRQASKC (SEQ ID NO:3) and the amino acid sequence CKSAQRHFRTGDEEPVN (SEQ ID NO:4).7. The method according to claim 6 , wherein the dyslipidemia is selected from a group of hyperlipidemias consisting of type I claim 6 , type II claim 6 , type III claim 6 , type IV claim 6 , or type V hyperlipidemia claim 6 , secondary hypertriglyceridemia claim 6 , secondary hypercholesterolemia claim 6 , hypercholesterolemia claim 6 , familial hypercholesterolemia claim 6 , familial combined hyperlipidemia ...

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20-06-2019 дата публикации

NOVEL VIBRIO ANGUILLARUM BACTERIOPHAGE VIB-ANP-1 AND USE THEREOF FOR INHIBITING PROLIFERATION OF VIBRIO ANGUILLARUM BACTERIA

Номер: US20190183945A1
Принадлежит:

The present invention relates to Siphoviridae bacteriophage Vib-ANP-1 (accession number KCTC 13075BP) having the ability to specifically kill bacteria and a genome represented by SEQ ID NO: 1 and isolated from nature, and a method for prevention or treatment of bacterial infection by using a composition containing the same bacteriophage as an effective ingredient. 1Vibrio anguillarum. A Siphoviridae bacteriophage Vib-ANP-1 (Accession number: KCTC 13075BP) isolated from nature , which has an ability to specifically kill and which includes a genome expressed by SEQ. ID. NO: 1.2Vibrio anguillarum. A composition for preventing and treating a infection , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'said bacteriophage Vib-ANP-1 (Accession number: KCTC 13075BP) of as an active ingredient.'}3Vibrio anguillarum. The composition for preventing and treating the infection of claim 2 , wherein said composition is used to prepare a medicine bath agent or a feed additive.4Vibrio anguillarum. A method for preventing or treating a infection claim 2 , the method comprising:{'claim-ref': {'@idref': 'CLM-00002', 'claim 2'}, 'administering to an animal other than a human the composition including the bacteriophage Vib-ANP-1 (Accession number: KCTC 13075BP) of as an active ingredient.'}5Vibrio anguillarum. The method for preventing or treating the infection of claim 4 , wherein said composition is administered to the animal other than the human for a use of a medicine bath agent or a feed additive. The present invention relates to a bacteriophage isolated from nature, which infects to thus kill , and a method for preventing and treating a infection using a composition including the same as an active ingredient. More particularly, the present invention relates to a Siphoviridae bacteriophage Vib-ANP-1 (Accession number: KCTC 13075BP) isolated from nature, which has the ability to specifically kill and which includes a genome expressed by SEQ. ID. NO: 1, and a method for ...

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05-07-2018 дата публикации

DIRECTED EVOLUTION THROUGH MUTATION RATE MODULATION

Номер: US20180187182A1
Автор: Reintjes Peter B.
Принадлежит:

The present invention relates to methods and systems for the directed evolution of macromolecules. The methods involve increasing the mutation rate of an evolving organism comprising a gene of interest that encodes a gene product lacking a desired activity, whereby a mutated gene of interest is produced that encodes an evolved gene product comprising the desired activity and causing a suppression of mutagenesis. The systems comprise an evolving organism comprising a gene of interest encoding a gene product to be evolved, a host organism, and optionally, a lagoon, a cellstat and/or a suitable growth medium. 1. A method of directed evolution of macromolecules , the method comprising increasing artificially the mutation rate experienced by a population of an evolving organism comprising a gene of interest to be evolved , wherein the gene of interest encodes a gene product that does not comprise a desired activity , whereby the gene of interest evolves in one or more of the evolving organisms so as to encode an evolved gene product comprising the desired activity , wherein the mutation rate decreases proportionally in response to the production of the evolved gene product comprising the desired activity , whereby the one or more evolving organisms comprising the evolved gene of interest are favored for reproduction in the population and at decreased mutation rate.2. The method of claim 1 , wherein the evolving organism requires a host organism to replicate.3. The method of claim 2 , wherein the host organism is engineered for an increased mutation rate claim 2 , relative to the mutation rate of a host organism that is not engineered for an increased mutation rate.4. The method of claim 3 , wherein increasing artificially the mutation rate experienced by the population of the evolving organism comprises contacting the population of the evolving organism with a population of the host organism claim 3 , wherein optionally the contacting occurs in a lagoon.5. The method of ...

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