Chimeric molecules

The invention relates to chimeric proteins comprising an antigen and a trimer forming portion or a trimer and virus-like particle forming portion of foamy virus envelope protein (FV TM). The trimer or trimer and virus-like particle forming portion comprises i) full length foamy virus transmembrane protein; ii) foamy virus transmembrane protein absent a functional cytoplasmic domain; iii) foamy virus transmembrane protein absent a functional cytoplasmic domain and transmembrane domain; iv) foamy virus ectodomain comprising N-terminal heptad repeat region and cysteine rich region between N-terminal heptad repeat region and C-terminal α-helical region; v) N-terminal heptad repeat region; vi) a functional variant of any one of i) to v); or vii) any one of i) to vi) lacking an FV fusion peptide domain. In particular, the antigen is an antigen of a virus envelope protein, such as HIV gp 120. Soluble and membrane bound forms of trimeric and higher oligomeric forms of the chimeric proteins are provided as well as nucleic acid molecules encoding and expressing same, viral-like particles comprising same, compositions including pharmaceutical compositions, host cells and kits. Methods are described for producing immune responses including antibodies determined by the chimeric protein or VLP, as well as methods of screening using the chimeric protein, VLP and/or antibodies.

FOAMY VIRAL VECTOR COMPOSITIONS AND METHODS FOR THE MANUFACTURE OF SAME

Disclosed are methods of preparing FV vector particles. In some aspects, the disclosed methods may include the steps of transfecting a population of eukaryotic cells by contacting said population of eukaryotic cells with one or more transfection reagents to form a transfection mixture, and incubating the transfection mixture to form a transfected cell population; harvesting the FV vector particles from said transfected cell population; purifying the FV vector particles; and concentrating the FV vector particles. 1. A method of preparing FV vector particles , comprising the steps of:a. transfecting a population of eukaryotic cells by contacting said population of eukaryotic cells with one or more transfection reagents to form a transfection mixture, and incubating said transfection mixture to form a transfected cell population;b. harvesting said FV vector particles from said transfected cell population, wherein said harvesting step is carried out about 70 hours to about 100 hours, or about 70 hours to about 90 hours, or about 70 hours to about 80 hours, or about 72 hours to about 75 hours, post-transfection;c. purifying said FV vector particles;d. concentrating said FV vector particles.2. The method of wherein said population of eukaryotic cells are pre-seeded for about 20 to about 30 hours claim 1 , or about 24 hours claim 1 , prior to said transfecting step.3. The method of wherein said pre-seeding is carried out until said population of eukaryotic cells achieves a cell density of from about 1×10cells/cmto about 2×10cells/cmor about 1.8×10cells/cm.4. The method of claim 1 , wherein said pre-seeding step comprises the step of plating eukaryotic cells 1 day prior to PEI transfection with fresh media.5. The method of wherein said pre-seeding step comprises adding poly-L-lysine in an amount sufficient to pre-coat tissue culture plastic with about 3.5 to about 10 mL per 225 cmsurface area claim 1 , preferably at a concentration of about 0.01%.6. The method of wherein ...

FOAMY VIRUSES AND METHODS OF USE

This document provides methods and materials for treating cancer. For example, foamy viruses (e.g., simian foamy viruses) are provided as well as methods and materials for treating cancer using foamy viruses as an oncolytic agent. 1. A chimeric simian foamy virus (SFV) comprising:a first genomic fragment of a first SFV strain; anda second genomic fragment of a second SFV strain.2. The chimeric SFV of claim 1 , wherein said first SFV strain is a first chimpanzee SFV strain claim 1 , and wherein said second SFV strain is a second chimpanzee SFV strain different from said first chimpanzee SFV strain.3. The chimeric SFV of claim 1 , wherein said first SFV strain and said second SFV strain are serotypically distinct.4. The chimeric SFV of claim 1 , wherein said first SFV strain is a chimpanzee PAN1 SFV strain claim 1 , and wherein said second SFV strain is a chimpanzee PAN2 SFV strain.5. The chimeric SFV of claim 1 , wherein said first genomic fragment of said first SFV strain comprises a 5′ LTR claim 1 , a nucleic acid encoding a gag polypeptide claim 1 , and a 5′ portion of a nucleic acid encoding pol polypeptide claim 1 , and wherein said second genomic fragment of said second SFV strain comprises a 3′ portion of a nucleic acid encoding a pol polypeptide claim 1 , a nucleic acid encoding a env polypeptide claim 1 , a nucleic acid encoding a tas polypeptide claim 1 , a nucleic acid encoding a bel2 polypeptide claim 1 , and a 3′ LTR.6. The chimeric SFV of claim 5 , wherein said 5′ portion of said nucleic acid encoding said pol polypeptide and said 3′ portion of said nucleic acid encoding said pol polypeptide are separated by a SfiI restriction site in the pol polypeptide.7. The chimeric SFV of claim 1 , wherein said chimeric SFV further comprises a transgene.811-. (canceled)12. The chimeric SFV of claim 7 , wherein said transgene encodes a receptor.13. The chimeric SFV of claim 12 , wherein said receptor is a chimeric antigen receptor (CAR).14. The chimeric SFV of claim ...

VECTOR ENCODING THERAPEUTIC POLYPEPTIDE AND SAFETY ELEMENTS TO CLEAR TRANSDUCED CELLS

A composition comprising: a stably integrating delivery vector; a modified mammalian thymidylate kinase (tmpk) activator polynucleotide wherein the modified mammalian tmpk polynucleotide encodes a modified mammalian tmpk polypeptide that increases phosphorylation of a prodrug relative to phosphorylation of the prodrug by wild-type mammalian tmpk polypeptide to a drug; and/or a targeting polynucleotide encoding a cell surface polypeptide that selectively binds a toxic binding agent. The disclosure also relates to use of these compositions in methods of treatment of diseases such as Fabry disease. 2. A composition comprising:a. a stably integrating delivery vector;b. an activator polynucleotide encoding a polypeptide that converts a prodrug to a drug;c. a docking polynucleotide encoding a docking polypeptide that selectively binds an antibody or an antibody conjugated with a toxic agent; andd. a therapeutic α-galactosidase A polynucleotide.3. The composition of claim 2 , wherein the activator polynucleotide comprises a tmpk polynucleotide with at least 80% sequence identity to a modified tmpk polynucleotide.4. The composition of or claim 2 , wherein the polynucleotide comprises a mammalian polynucleotide claim 2 , optionally a human polynucleotide claim 2 , and the polypeptide comprise a mammalian polypeptide claim 2 , optionally a human polypeptide.5. The composition any one of to claim 2 , wherein the activator polynucleotide comprises a modified mammalian tmpk polynucleotide encoding a modified mammalian tmpk polypeptide that increases phosphorylation of a prodrug relative to phosphorylation of the prodrug by wild-type mammalian tmpk polypeptide claim 2 , optionally the modified mammalian tmpk polynucleotide comprises a mammalian tmpk polynucleotide with a point mutation or multiple mutations.6. The composition of claim 5 , wherein the point mutation comprises a mutation in a codon of the polynucleotide selected from the group consisting of a mutation that encodes ...

FOAMY VIRAL VECTOR COMPOSITIONS AND METHODS FOR THE MANUFACTURE OF SAME

Disclosed are methods of preparing FV vector particles. In some aspects, the disclosed methods may include the steps of transfecting a population of eukaryotic cells by contacting said population of eukaryotic cells with one or more transfection reagents to form a transfection mixture, and incubating the transfection mixture to form a transfected cell population; harvesting the FV vector particles from said transfected cell population; purifying the FV vector particles; and concentrating the FV vector particles. 1. A method of preparing FV vector particles , comprising the steps of:a. transfecting a population of eukaryotic cells by contacting said population of eukaryotic cells with one or more transfection reagents to form a transfection mixture, and incubating said transfection mixture to form a transfected cell population;b. harvesting said FV vector particles from said transfected cell population, wherein said harvesting step is carried out about 70 hours to about 100 hours, or about 70 hours to about 90 hours, or about 70 hours to about 80 hours, or about 72 hours to about 75 hours, post-transfection;c. purifying said FV vector particles;d. concentrating said FV vector particles.2. The method of wherein said population of eukaryotic cells are pre-seeded for about 20 to about 30 hours claim 1 , or about 24 hours claim 1 , prior to said transfecting step.3. The method of wherein said pre-seeding is carried out until said population of eukaryotic cells achieves a cell density of from about 1×10cells/cmto about 2×10cells/cmor about 1.8×10cells/cm.4. The method of claim 1 , wherein said pre-seeding step comprises the step of plating eukaryotic cells 1 day prior to PEI transfection with fresh media.5. The method of wherein said pre-seeding step comprises adding poly-L-lysine in an amount sufficient to pre-coat tissue culture plastic with about 3.5 to about 10 mL per 225 cmsurface area claim 1 , preferably at a concentration of about 0.01%.6. The method of wherein ...

Rna based method to obtain stably integrated retroviral vectors

The present invention relates to viral transformation method, particularly foamy virus-mediated transformation method. The present invention relates to the transfer of transgene into cells by the safe and efficient transfer of RNA encoding foamy components. The present invention has therefore therapeutic interest, especially in the field of gene therapy.

FOAMY VIRAL VECTOR COMPOSITIONS AND METHODS FOR THE MANUFACTURE OF SAME

Disclosed are methods of preparing FV vector particles. In some aspects, the disclosed methods may include the steps of transfecting a population of eukaryotic cells by contacting said population of eukaryotic cells with one or more transfection reagents to form a transfection mixture, and incubating the transfection mixture to form a transfected cell population; harvesting the FV vector particles from said transfected cell population; purifying the FV vector particles; and concentrating the FV vector particles. 1. A method of preparing FV vector particles , comprising the steps of:a. transfecting a population of eukaryotic cells by contacting said population of eukaryotic cells with one or more transfection reagents to form a transfection mixture, and incubating said transfection mixture to form a transfected cell population;b. harvesting said FV vector particles from said transfected cell population, wherein said harvesting step is carried out about 70 hours to about 100 hours, or about 70 hours to about 90 hours, or about 70 hours to about 80 hours, or about 72 hours to about 75 hours, post-transfection;c. purifying said FV vector particles;d. concentrating said FV vector particles.2. The method of wherein said population of eukaryotic cells are pre-seeded for about 20 to about 30 hours claim 1 , or about 24 hours claim 1 , prior to said transfecting step.3. The method of wherein said pre-seeding is carried out until said population of eukaryotic cells achieves a cell density of from about 1×10cells/cmto about 2×10cells/cmor about 1.8×10cells/cm.4. The method of claim 1 , wherein said pre-seeding step comprises the step of plating eukaryotic cells 1 day prior to PEI transfection with fresh media.5. The method of wherein said pre-seeding step comprises adding poly-L-lysine in an amount sufficient to pre-coat tissue culture plastic with about 3.5 to about 10 mL per 225 cmsurface area claim 1 , preferably at a concentration of about 0.01%.6. The method of wherein ...

Simian adenovirus nucleic acid and amino acid sequences, vectors containing same, and methods of use

A recombinant vector comprises simian adenovirus sequences and a heterologous gene under the control of regulatory sequences. A cell line which expresses simian adenovirus gene(s) is also disclosed. Methods of using the vectors and cell lines are provided.

EUKARYOTIC CELL LINES FOR PACKAGING RECOMBINANT RETROVIRAL RNAs BY TRANSCOMPLEMENTATION, AND EXPRESSION VECTORS FOR USE IN SAID TRANSCOMPLEMENTATION

The present invention relates to novel cell lines, so-called transcomplementation cell lines, which enable the packaging of recombinant retroviral RNAs carrying nucleotide sequences of interest. The present invention aims at transferring and expressing these sequences in eucaryotic target cells. The invention also related to expression vectors for the transcomplementation of defective retroviral vectors.

Simian adenovirus nucleic acid and amino acid sequences, vectors containing same, and methods of use

A recombinant vector comprises simian adenovirus sequences and a heterologous gene under the control of regulatory sequences. A cell line which expresses simian adenovirus gene(s) is also disclosed. Methods of using the vectors and cell lines are provided.

Simian adenovirus nucleic acid and amino acid sequences, vectors containing same, and methods of use

A recombinant vector comprises simian adenovirus sequences and a heterologous gene under the control of regulatory sequences. A cell line which expresses simian adenovirus gene(s) is also disclosed. Methods of using the vectors and cell lines are provided.

Simian adenovirus nucleic acid and amino acid sequences, vectors containing same, and methods of use

A recombinant vector comprises simian adenovirus sequences and a heterologous gene under the control of regulatory sequences. A cell line which expresses simian adenovirus gene(s) is also disclosed. Methods of using the vectors and cell lines are provided.

Simian adenovirus adsv1 nucleic acid and amino acid sequences, vectors containing same, and methods of use

A recombinant vector comprises simian adenovirus AdSV1 sequences and a heterologous gene under the control of regulatory sequences. A cell line which expresses simian adenovirus gene(s) is also disclosed. Methods of using the vectors and cell lines are provided.

Simian adenovirus nucleic acid and amino acid sequences, vectors containing same, and methods of use

재조합체 벡터는 조절 서열의 조절하에 원숭이 아데노바이러스 서열과 이종 유전자를 포함한다. 원숭이 아데노바이러스 유전자를 발현하는 세포주가 또한 개시되어 있다. 벡터와 세포주를 사용하는 방법이 제공된다. Recombinant vectors comprise monkey adenovirus sequences and heterologous genes under the control of regulatory sequences. Cell lines that express the monkey adenovirus genes are also disclosed. Methods of using vectors and cell lines are provided. 원숭이 아데노바이러스 서열, 이종 유전자, 재조합체 벡터 Monkey adenovirus sequence, heterologous gene, recombinant vector

Packaging cells and expression vectors for transcomplementation of deleted retroviral vectors

(57)【要約】 本発明は、標的細胞のゲノム内への、選択したヌクレオチド配列（導入遺伝子と呼ぶ）のトランスファー、及び／または組み込みを提供するレトロウイルスベクタのトランス補完用発現ベクタであって、以下を具備するものに関する：a)スプーマウイルスファミリーのレトロウイルスのエンベロープに由来するポリペプチド（ENVポリペプチド）をコードしている、envと呼ばれるヌクレオチド配列であって、該ポリペプチドENVはレトロウイルスRNAのカプシド化を提供する；b)配列envの発現を調節する転写制御シグナル。本発明は更に、上に開示したベクタとの組み換え体である、選択したヌクレオチド配列（導入遺伝子）の、標的細胞内へのトランスファー及び／または組み込みを提供する、組み換えレトロウイルスRNAのトランス補完によるカプシド化用の真核細胞にも関する。

Pseudotyping of foamy viruses

The present invention relates to means and methods for pseudotyping of foamy viruses and the pharmaceutical application of pseudotyped foamy virus particles. The invention is applicable in biomedical research and in diagnostic and therapeutic applications. One aspect of the invention is a fusion protein comprising a foamy virus capsid (Gag) protein and a first dimerization domain that is applicable to dimerize with a second dimerization domain from another protein upon binding of a small molecule ligand to both the first and the second dimerization domain. Another aspect of the invention is a fusion protein comprising an envelope (Env) protein not derived from foamy virus and a second dimerization domain that is applicable to dimerize with a first dimerization domain from another protein upon binding of a small molecule ligand to both the first and the second dimerization domain. Another aspect of the invention is a fusion protein comprising a membrane-targeting domain not derived from foamy virus, and a second dimerization domain that is applicable to dimerize with a first dimerization domain from another protein upon binding of a small molecule ligand to both the first and the second dimerization domain.

ENCAPSIDATION LINES AND EXPRESSION VECTORS FOR TRANSCOMPLEMENTATION OF DEFECTIVE RETROVIRAL VECTORS

The invention relates to an expression vector for the transcomplementation of a retroviral vector which provides for the transfer and/or integration within the genome of a target cell, of a selected nucleotide sequence (called "transgenic sequence"), characterized in that it comprises; a) a nucleotide sequence called sequence <u>env</u>, coding for a polypeptide derived from the envelope (polypeptide ENV) of a retrovirus of the spumavirus family, the polypeptide ENV providing for the encapsidation of retroviral RNA, b) transcription regulating signals controlling the expression of the sequence <u>env</u>. The invention also relates to a eucaryotic cell for the encapsidation by transcomplementation of recombinant retroviral RNA providing for the transfer and/or integration within the genome of a target cell, of a selected nucleotide sequence (transgenic sequence) recombined with the above disclosed vector.

Chimeric molecules

The invention relates to chimeric proteins comprising an antigen and a trimer forming portion or a trimer and virus-like particle forming portion of foamy virus envelope protein (FV TM). The trimer or trimer and virus-like particle forming portion comprises i) full length foamy virus transmembrane protein; ii) foamy virus transmembrane protein absent a functional cytoplasmic domain; iii) foamy virus transmembrane protein absent a functional cytoplasmic domain and transmembrane domain; iv) foamy virus ectodomain comprising N-terminal heptad repeat region and cysteine rich region between N-terminal heptad repeat region and C-terminal α-helical region; v) N-terminal heptad repeat region; vi) a functional variant of any one of i) to v); or vii) any one of i) to vi) lacking an FV fusion peptide domain. In particular, the antigen is an antigen of a virus envelope protein, such as HIV gp120. Soluble and membrane bound forms of trimeric and higher oligomeric forms of the chimeric proteins are provided as well as nucleic acid molecules encoding and expressing same, viral-like particles comprising same, compositions including pharmaceutical compositions, host cells and kits. Methods are described for producing immune responses including antibodies determined by the chimeric protein or VLP, as well as methods of screening using the chimeric protein, VLP and/or antibodies.

Simian adenovirus nucleic acid and amino acid sequences, vectors containing same, and methods of use

A recombinant vector comprises simian adenovirus sequences and a heterologous gene under the control of regulatory sequences. A cell line which expresses simian adenovirus gene(s) is also disclosed. Methods of using the vectors and cell lines are provided.

Gene transfer into target cells in vivo comprises applying a gene transfer vector and a transduction enhancer at the same time and place

Gene transfer into target cells in vivo comprises applying a gene transfer vector and a transduction enhancer at the same time and place. Independent claims are also included for: (1) nonhuman mammal genetically modified by the above method; (2) the mixture of materials used in the above method. ACTIVITY : Anti-AIDS; Antidiabetic; Antianemic; Cytostatic. MECHANISM OF ACTION : Gene therapy.

Simian adenovirus nucleic acid and amino acid sequences, vectors containing same, and methods of use

A recombinant vector comprises simian adenovirus sequences and a heterologous gene under the control of regulatory sequences. A cell line which expresses simian adenovirus gene(s) is also disclosed. Methods of using the vectors and cell lines are provided.

Methods and compositions for inhibition of membrane fusion-associated events, including hiv transmission

The present invention relates to peptides which exhibit potent anti-retroviral activity. The peptides of the invention comprise DP178 (SEQ ID:1) peptide corresponding to amino acids 638 to 673 of the HIV-1LAI gp4l protein, and fragments, analogs and homologs of DP178. The invention further relates to the uses of such peptides as inhibitory of human and non-human retroviral, especially HIV, transmission to uninfected cells.

New spumavirus isolated from humans

The present invention comprises spumavirus isolated from humans. More specifically, the spumavirus of the present invention was isolated from humans who had exposure to nonhuman primates. Importantly, the spumavirus of the present invention or antibodies to the spumavirus can be used to detect the presence of spumavirus or antibodies in body fluids, for pathogenicity studies of related viruses, and as a vector for gene therapies. The spumavirus of the invention can also be used for treatment of conditions in humans due to the presence of rapidly dividing cells and for recombinant live virus vaccination.

Methods for inhibition of membrane fusion-associated events, including respiratory syncytial virus transmission

The present invention relates to peptides which exhibit potent anti-viral activity. In particular, the invention relates to methods of using such peptides as inhibitory of respiratory syncytial virus (“RSV”) transmission to uninfected cells. The peptides used in the methods of the invention are homologs of the DP-178 and DP-107 peptides, peptides corresponding to amino acid residues 638 to 673, and to amino acid residues 558 to 595, respectively, of the HIV-1 LAI transmembrane protein (TM) gp41.

Recombinant adenovirus, isolated host cell containing it, composition comprising the recombinant adenovirus and use

Det beskrives en rekombinant vektor omfattende simianadenovirussekvenser og heterologt gen under kontroll av regulatoriske sekvenser. Det beskrives videre en cellelinje som uttrykker ett eller flere simianadenovirusgener. Det beskrives fremgangsmåter for anvendelse av vektorene og cellelinjene.

Foamy viruses and methods of use

The disclosure provides methods and materials for treating cancer. For example, foamy viruses (e.g., simian foamy viruses) are provided as well as methods and materials for treating cancer using foamy viruses as an oncolytic agent. Specifically, the disclosure provides a chimeric simian foamy virus (SFV) comprising: a first genomic fragment of a first SFV strain; and a second genomic fragment of a second SFV strain. Further provided are methods for treating a mammal having cancer comprising administering to said mammal SFV having oncolytic anticancer activity.

Chimeric molecules

The invention relates to chimeric proteins comprising an antigen and a trimer forming portion or a trimer and virus-like particle forming portion of foamy virus envelope protein (FV TM). The trimer or trimer and virus-like particle forming portion comprises i) full length foamy virus transmembrane protein; ii) foamy virus transmembrane protein absent a functional cytoplasmic domain; iii) foamy virus transmembrane protein absent a functional cytoplasmic domain and transmembrane domain; iv) foamy virus ectodomain comprising N-terminal heptad repeat region and cysteine rich region between N-terminal heptad repeat region and C-terminal α-helical region; v) N-terminal heptad repeat region; vi) a functional variant of any one of i) to v); or vii) any one of i) to vi) lacking an FV fusion peptide domain. In particular, the antigen is an antigen of a virus envelope protein, such as HIV gp120. Soluble and membrane bound forms of trimeric and higher oligomeric forms of the chimeric proteins are provided as well as nucleic acid molecules encoding and expressing same, viral-like particles comprising same, compositions including pharmaceutical compositions, host cells and kits. Methods are described for producing immune responses including antibodies determined by the chimeric protein or VLP, as well as methods of screening using the chimeric protein, VLP and/or antibodies.

Expression of a foamy virus envelope protein

The invention concerns constructs for the expression of a protein comprising at least a modified FV envelope protein, the protein so obtained as well as the complementation cell line permitting the production of pseudotyped viral particle. It also concerns pharmaceutical composition comprising said particles and a method for treating a disease.

Recombinant foamy virus vectors for medicinal and diagnostic uses, and processes for preparing recombinant foamy virus vectors

The present invention relates to the preparation of novel vector systems which are generated by in-vitro recombina-tion, using gene technology, of nucleic acids from foamy virus species and of exogenous nucleic acid, and are produced by suitable host cells or by recombinantly altered packaging cell lines. The recombinant preparation of particularly suitable packaging cell lines is likewise a constituent of this invention. The invention is distin-guished by the safe and efficient transfer by foamy virus vectors of therapeutic and other genes into eukaryotic cells.

Simian adenovirus nucleic acid and amino acid sequences, vectors containing same, and methods of use

A recombinant vector comprises simian adenovirus sequences and a heterologous gene under the control of regulatory sequences. A cell line which expresses simian adenovirus gene(s) is also disclosed. Methods of using the vectors and cell lines are provided.

Simian adenovirus nucleic acid and amino acid sequences, vectors containing same, and methods of use

一种含猿猴腺病毒序列和在调控序列控制下的异源基因的重组载体。还公开了一种能表达猿猴腺病毒基因的细胞系。提供了利用此载体和细胞系的方法。

Live replicating spumavirus vector

The present invention provides a vector or vector containing composition comprising a spumavirus backbone and a antigen-encoding nucleic acid. The present invention also provides methods of treating or preventing a condition resulting from a viral, bacterial, or parasitic infection in a subject comprising administering to the subject an effective amount of the vector or vector containing composition comprising a spumavirus backbone and an antigen-encoding nucleic acid. Also provided in the present invention are methods of treating a condition resulting from a cancer in a subject comprising administering to the subject an effective amount of the vector or vector containing composition comprising a spumavirus backbone and an antigen-encoding nucleic acid.

EXPRESSION OF A MODIFIED "FOAMY VIRUS ENVELOPE PROTEIN" (SLEEP PROTEIN)

Recombinant foamy virus vectors for medicinal and diagnostic uses, and processes for preparing recombinant foamy virus vectors

The present invention relates to the preparation of novel vector systems which are generated by in-vitro recombina-tion, using gene technology, of nucleic acids from foamy virus species and of exogenous nucleic acid, and are produced by suitable host cells or by recombinantly altered packaging cell lines. The recombinant preparation of particularly suitable packaging cell lines is likewise a constituent of this invention. The invention is distin-guished by the safe and efficient transfer by foamy virus vectors of therapeutic and other genes into eukaryotic cells.

Simian adenovirus nucleic acid and amino acid sequences, vectors containing same, and methods of use

A recombinant vector comprises simian adenovirus sequences and a heterologous gene under the control of regulatory sequences. A cell line which expresses simian adenovirus gene(s) is also disclosed. Methods of using the vectors and cell lines are provided.

Recombinant foamy virus vectors for medicinal and diagnostic uses, and processes for preparing recombinant foamy virus vectors

The present invention relates to the preparation of novel vector systems which are generated by in-vitro recombination, using gene technology, of nucleic acids from foamy virus species and of exogenous nucleic acid, and are produced by suitable host cells or by recombinantly altered packaging cell lines. The recombinant preparation of particularly suitable packaging cell lines is likewise a constituent of this invention. The invention is distinguished by the safe and efficient transfer by foamy virus vectors of therapeutic and other genes into eukaryotic cells.

Expression of a foamy virus envelope protein

Simian adenovirus nucleic acid and amino acid sequences, vectors containing same, and methods of use

A recombinant vector comprises simian adenovirus sequences and a heterologous gene under the control of regulatory sequences. A cell line which expresses simian adenovirus gene(s) is also disclosed. Methods of using the vectors and cell lines are provided.

Compositions for inhibition of membrane fusion-associated events, including human parainfluenza virus transmission

The present invention relates to peptides which exhibit potent anti-retroviral activity. The peptides of the invention comprise DP178 (SEQ ID NO:1) peptide corresponding to amino acids 638 to 673 of the HIV-1 LAI gp41 protein, and fragments, analogs and homologs of DP178. The invention further relates to the uses of such peptides as inhibitory of human and non-human retroviral, especially HIV, transmission to uninfected cells.

Expression of a foamy virus envelope protein

The invention concerns constructs for the expression of a protein comprising at least a modified FV envelope protein, the protein so obtained as well as the complementation cell line permitting the production of pseudotyped viral particle. It also concerns pharmaceutical composition comprising said particles and a method for treating a disease.

Vector encoding therapeutic polypeptide and safety elements to clear transduced cells

A composition comprising: a stably integrating delivery vector; an modified mammalian thymidylate kinase (tmpk) activator polynucleotide wherein the modified mammalian tmpk polynucleotide encodinges a modified mammalian tmpk polypeptide that increases phosphorylation of converts a prodrug relative to phosophorylation of the prodrug by wild-type mammalian tmpk polypeptideto a drug; and/or a targeting polynucleotide encoding a cell surface polypeptide that selectively binds a toxic binding agent. The invention also relates to use of these compositions in methods of treatment of diseases such as Fabry disease.

Composition and method for treating viral infection

Methods for inhibiting virus propagation and treating virus infection are provided which include administering to cells infected with viruses a compound capable of inhibiting viral budding from the cells.

Beta-2 microglobulin-deficient cells

The invention provides isolated primate cells preferably human cells that comprise a genetically engineered disruption in a beta-2 microglobulin (B2 M) gene, which results in deficiency in MHC class I expression and function. Also provided are the method of using the cells for transplantation and treating a disease condition.

Composition and method for treating viral infection

Methods for inhibiting virus propagation and treating virus infection are provided which include administering to cells infected with viruses a compound capable of inhibiting viral budding from the cells.

Optimized vaccines to provide protection against ebola and other viruses

EXPRIMIERUNG EINES MODIFIZIERTEM ßFOAMY VIRUS ENVELOPE PROTEINß (HÜLLENPROTEIN)

Beta-2 microglobulin-deficient cells

The invention provides isolated primate cells preferably human cells that comprise a genetically engineered disruption in a beta-2 microglobulin (B2M) gene, which results in deficiency in MHC class I expression and function. Also provided are the method of using the cells for transplantation and treating a disease condition.

Simian adenovirus nucleic acid and amino acid sequences, vectors containing same, and methods of use

Verpackungszellinie zur transkomplementierung von defektiven retroviren-vektoren

Hiv-1- und hiv-2-peptide zur hemmung von mit membranfusionen in zusammenhang stehenden phänomenen, einschliesslich der übertragung von hiv

Optimzed vaccines to provide protection against ebola and other viruses

The invention is related to a nucleic acid molecule comprising a polynucleotide encoding a modified filovirus glycoprotein (GP) having at least one amino acid change located in a relatively conserved region of said GP that decreases in vitro cytotoxicity and retains immunogenicity when compared to in vitro cytotoxicity and immunogenicity of a wild type filovirus GP, and related modified filovirus GPs, plasmid DNAs, recombinant viruses, adenoviruses, pharmaceutical compositions, vaccine compositions, antibodies that are specifically reactive with the modified filovirus GPs, and related methods of making and using the same.

Optimized vaccines to provide protection against ebola and other viruses

The invention is related to a nucleic acid molecule comprising a polynucleotide encoding a modified filovirus glycoprotein (GP) having at least one amino acid change located in a relatively conserved region of said GP that decreases in vitro cytotoxicity and retains immunogenicity when compared to in vitro cytotoxicity and immunogenicity of a wild type filovirus GP, and related modified filovirus GPs, plasmid DNAs, recombinant viruses, adenoviruses, pharmaceutical compositions, vaccine compositions, antibodies that are specifically reactive with the modified filovirus GPs, and related methods of making and using the same.

Optimized vaccines to provide protection against Ebola and other viruses

Optimized vaccines to provide protection against ebola and other viruses

The invention is related to a nucleic acid molecule comprising a polynucleotide encoding a modified filovirus glycoprotein (GP) having at least one amino acid change located in a relatively conserved region of said GP that decreases in vitro cytotoxicity and retains immunogenicity when compared to in vitrocytotoxicity and immunogenicity of a wild type filovirus GP, and related modified filovirus GPs, plasmid DNAs, recombinant viruses, adenoviruses, pharmaceutical compositions, vaccine compositions, antibodies that are specifically reactive with the modified filovirus GPs, and related methods of making and using the same.

Isolation of a human retrovirus

The present invention comprises compositions and methods comprising a spumavirus isolated from a human. More specifically, the spumavirus of the present invention was isolated from a human who had exposure to nonhuman primates. Importantly, the methods and compositions of the present invention comprising the spumavirus and including antibodies to the spumavirus, can be used to detect the presence of spumavirus or antibodies in body fluids, for pathogenicity studies of related viruses, and as a vector for gene therapies. The present invention can also be used for treatment of conditions in humans due to the presence of rapidly dividing cells and for recombinant live virus vaccination.

Retrovirus isolated from humans

The present invention comprises spumavirus isolated from humans. More specifically, the spumavirus of the present invention was isolated from humans who had exposure to nonhuman primates. Importantly, the spumavirus of the present invention or antibodies to the spumavirus can be used to detect the presence of spumavirus or antibodies in body fluids, for pathogenicity studies of related viruses, and as a vector for gene therapies. The spumavirus of the invention can also be used for treatment of conditions in humans due to the presence of rapidly dividing cells and for recombinant live virus vaccination.

Use of the foamy virus bet protein for inactivating apobec

Described is the foamy virus Bet-mediated inactivation of the mutagenic, genome-modifying and vector-inactivating cellular enzyme ABOBEC. Such inactivation is useful for the treatment or prevention of various disease, e.g., cancer, or for enhancing the production and genetic stability of gene therapy vectors, preferably retroviral vectors.

Spumavirus isolated from humans

The present invention comprises a spumavirus isolated from a human. More specifically, the spumavirus of the present invention was isolated from a human who had exposure to nonhuman primates. Importantly, the spumavirus of the present invention or antibodies to the spumavirus can be used to detect the presence of spumavirus or antibodies in body fluids, for pathogenicity studies of related viruses, and as a vector for gene therapies. The spumavirus of the invention can also be used for treatment of conditions in humans due to the presence of rapidly dividing cells and for recombinant live virus vaccination.

Rekombinante foamy-virus-vektoren zur medizinischen und diagnostischen verwendung und verfahren zur herstellung rekombinanter foamy- virus-vektoren

2-플라스미드 시스템으로 제조된 가짜 포미 바이러스 및 이의 용도

본 발명은 2-플라스미드 시스템으로 제조된 가짜 포미 바이러스에 관한 것이다. 본 발명에 따른 2-플라스미드 시스템은 종래 기술에서 3개 이상의 보조 플라스미드를 이용하는 것에 비해 현저히 적은 수의 보조 플라스미드를 이용하므로, 시스템 생산에 대한 경제적이라는 장점이 있다. 또한 상기 2-플라스미드 시스템을 통해 제조된 가짜 포미 바이러스는 표적세포에 단회 감염되며, 이후 표적 세포 내에서 생산된 바이러스는 감염성이 없는 것을 확인하였다. 뿐만 아니라 상기 가짜 포미 바이러스에 의해 도입된 외부 유전자는 안정적이고 영구적으로 발현되는 것을 확인하였다. 따라서 본 발명의 2-플라스미드 시스템 및 이에 의해 생산된 가짜 포미 바이러스는 외부 단백질 발현 분야; 유전병 치료 분야; 및 백신 분야;에서 다양하게 활용될 수 있다.

Foamy virus mutant reverse transcriptase

Trennung eines humanen retrovirus

一种泡沫病毒包装载体系统及其构建方法和试剂盒

本申请涉及生物技术领域，尤其是涉及一种泡沫病毒包装载体系统及其构建方法和试剂盒。本申请采用五质粒法进行泡沫病毒包毒，获得感染能力明显增强、生产滴度明显增加的泡沫病毒包装载体系统。其中，本申请在优化的辅助质粒A、辅助质粒B、辅助质粒C的基础上(所述辅助质粒A的核苷酸序列如SEQ ID NO:1所示；所述辅助质粒B的核苷酸序列如SEQ ID NO:2所示；所述辅助质粒C的核苷酸序列如SEQ ID NO:3所示)，在泡沫病毒包装过程中额外加入外源糖蛋白质粒能够有效提高泡沫病毒侵染细胞效率，从而达到滴度的提升，并且还能降低生产成本的同时提高泡沫病毒的应用价值。

Foamy virus mutant reverse transcriptase

The present invention relates to a highly processive reverse transcriptase having DNA polymerase activity and substantially reduced protease activity. More specifically, the invention relates to an isolated reverse transcriptase from foamy virus comprising a substantially inactivated protease. The invention also relates to vectors containing the gene and hosts transformed with the vector of the invention. Further, the invention relates to a method for producing reverse transcriptase having DNA polymerase activity and substantially reduced protease activity by expressing the reverse transcriptase genes of the present invention in a recombinant host. Methods are also provided for producing cDNA from polynucleotides using the highly processive reverse transcriptase of the invention. Kits for the preparation of cDNA from RNA comprising the highly processive reverse transcriptase of the invention are also provided.

Minimales retrovirus-vektorsystem

Die vorliegende Erfindung betrifft ein Retrovirus-Vektorsystem mit einem Transfervektor, enthaltend mindestens eine Expressionskassette zur Aufnahme einer für ein in Bezug auf dasbetreffende Retrovirus heterologes, insbesondere nicht- retrovirales Genprodukt codierenden Nukleotidsequenz,der dadurch gekennzeichnet ist, dass er keine Sequenzen des betreffenden Retrovirus enthält. Weitere Gegenstände der vorliegenden Erfindung betreffen Wirtszellen, die mit dem Vektorsystem transfiziert sind, Verfahren zur Herstellung der Wirtszellen, ein Kit zur Expression eines in den Bezug auf das betreffende Retrovirus heterologen, insbesondere nicht-retroviralen Genprodukts, dass das Vektorsystem enthält, sowie ein Verfahren zur Expression eines in Bezug auf das betreffende Retrovirus heterologen, insbesondere nicht-retroviralen Genprodukts in einer Zelle unter Verwendung des Vektorsystems.

Spumavirus isolated from humans

The present invention comprises a spumavirus isolated from a human. More specifically, the spumavirus of the present invention was isolated from a human who had exposure to nonhuman primates. Importantly, the spumavirus of the present invention or antibodies to the spumavirus can be used to detect the presence of spumavirus or antibodies in body fluids, for pathogenicity studies of related viruses, and as a vector for gene therapies. The spumavirus of the invention can also be used for treatment of conditions in humans due to the presence of rapidly dividing cells and for recombinant live virus vaccination.

Retrovirus isolated from humans

The present invention comprises spumavirus isolated from humans. More specifically, the spumavirus of the present invention was isolated from humans who had exposure to nonhuman primates. Importantly, the spumavirus of the present invention or antibodies to the spumavirus can be used to detect the presence of spumavirus or antibodies in body fluids, for pathogenicity studies of related viruses, and as a vector for gene therapies. The spumavirus of the invention can also be used for treatment of conditions in humans due to the presence of rapidly dividing cells and for recombinant live virus vaccination.

Retrovirus isolated from humans

Retrovirus isolated from humans

The present invention comprises spumavirus isolated from humans. More specifically, the spumavirus of the present invention was isolated from humans who had exposure to nonhuman primates. Importantly, the spumavirus of the present invention or antibodies to the spumavirus can be used to detect the presence of spumavirus or antibodies in body fluids, for pathogenicity studies of related viruses, and as a vector for gene therapies. The spumavirus of the invention can also be used for treatment of conditions in humans due to the presence of rapidly dividing cells and for recombinant live virus vaccination.

Retrovirus isolated from humans

The present invention comprises spumavirus isolated from humans. More specifically, the spumavirus of the present invention was isolated from humans who had exposure to nonhuman primates. Importantly, the spumavirus of the present invention or antibodies to the spumavirus can be used to detect the presence of spumavirus or antibodies in body fluids, for pathogenicity studies of related viruses, and as a vector for gene therapies. The spumavirus of the invention can also be used for treatment of conditions in humans due to the presence of rapidly dividing cells and for recombinant live virus vaccination.

Use of the foamy virus bet protein for inactivating apobec

Described is the foamy virus Bet-mediated inactivation of the mutagenic, genome-modifying and vector-inactivating cellular enzyme ABOBEC. Such inactivation is useful for the treatment or prevention of various disease, e.g., cancer, or for enhancing the production and genetic stability of gene therapy vectors, preferably retroviral vectors.

Beta-2 microglobulin-deficient cells

The invention provides isolated primate cells preferably human cells that comprise a genetically engineered disruption in a beta-2 microglobulin (B2M) gene, which results in deficiency in MHC class I expression and function. Also provided are the method of using the cells for transplantation and treating a disease condition.

一种泡沫病毒包装载体系统及其构建方法和试剂盒

本申请涉及生物技术领域，尤其是涉及一种泡沫病毒包装载体系统及其构建方法和试剂盒。本申请采用五质粒法进行泡沫病毒包毒，获得感染能力明显增强、生产滴度明显增加的泡沫病毒包装载体系统。其中，本申请在优化的辅助质粒A、辅助质粒B、辅助质粒C的基础上(所述辅助质粒A的核苷酸序列如SEQ ID NO:1所示；所述辅助质粒B的核苷酸序列如SEQ ID NO:2所示；所述辅助质粒C的核苷酸序列如SEQ ID NO:3所示)，在泡沫病毒包装过程中额外加入外源糖蛋白质粒能够有效提高泡沫病毒侵染细胞效率，从而达到滴度的提升，并且还能降低生产成本的同时提高泡沫病毒的应用价值。

Foamyvirus vectors and methods of use

The disclosure of the present application provides foamyvirus vectors, as well as methods and kits involving the same. In at least one embodiment, a plurality of recombinant vectors comprises an expression sequence encoding at least one component of a foamyvirus particle, wherein at least one codon of the expression sequence is optimized for expression in homo sapiens.

Foamy virus mutant reverse transcriptase

The present invention relates to a highly processive reverse transcriptase having DNA polymerase activity and substantially reduced protease activity. More specifically, the invention relates to an isolated reverse transcriptase from foamy virus comprising a substantially inactivated protease. The invention also relates to vectors containing the gene and hosts transformed with the vector of the invention. Further, the invention relates to a method for producing reverse transcriptase having DNA polymerase activity and substantially reduced protease activity by expressing the reverse transcriptase genes of the present invention in a recombinant host. Methods are also provided for producing cDNA from polynucleotides using the highly processive reverse transcriptase of the invention. Kits for the preparation of cDNA from RNA comprising the highly processive reverse transcriptase of the invention are also provided.

Cytochrome p450 suicide gene system

The invention relates to a modified human CYP4B1 protein and a nucleic acid encoding for the modified human CYP4B1 protein. The invention further relates to an expression vector comprising a nucleic acid encoding for a modified human CYP4B1 protein, as well as to a cell comprising a modified CYP4B1 protein. In addition, the invention relates to a modified human CYP4B1 protein for use in treating transplantation induced graft- versus-host-disease (GvHD), and to 4-ipomeanol (4-IPO) for use in killing a cell.

Retrovirus isolated from humans

The present invention comprises spumavirus isolated from humans. More specifically, the spumavirus of the present invention was isolated from humans who had exposure to nonhuman primates. Importantly, the spumavirus of the present invention or antibodies to the spumavirus can be used to detect the presence of spumavirus or antibodies in body fluids, for pathogenicity studies of related viruses, and as a vector for gene therapies. The spumavirus of the invention can also be used for treatment of conditions in humans due to the presence of rapidly dividing cells and for recombinant live virus vaccination.

Isolation of a human retrovirus

The present invention comprises compositions and methods comprising a spumavirus isolated from a human. More specifically, the spumavirus of the present invention was isolated from a human who had exposure to nonhuman primates. Importantly, the methods and compositions of the present invention comprising the spumavirus and including antibodies to the spumavirus, can be used to detect the presence of spumavirus or antibodies in body fluids, for pathogenicity studies of related viruses, and as a vector for gene therapies. The present invention can also be used for treatment of conditions in humans due to the presence of rapidly dividing cells and for recombinant live virus vaccination.

Rna based method to obtain stably integrated retroviral vectors

The present invention relates to viral transformation method, particularly foamy virus-mediated transformation method. The present invention relates to the transfer of transgene into cells by the safe and efficient transfer of RNA encoding foamy components. The present invention has therefore therapeutic interest, especially in the field of gene therapy.

Composition and method for treating viral infection

Methods for inhibiting virus propagation and treating virus infection are provided which include administering to cells infected with viruses a compound capable of inhibiting viral budding from the cells.

Re-targeted foamy virus vectors

Provided herein are retargeted foamy virus (FV) vectors, including insulated retargeted FV vectors such as 650cHS4, Al, and A2 insulator retargeted FV vectors that exhibit high, clinically significant titers, favorable safety profiles, and reduced genotoxicity. The retargeted FV vectors disclosed herein may be suitably employed for therapeutic applications, in particular gene therapy applications, which involve the ex vivo and/or in vivo delivery of a gene of interest to a wide variety of target cells, including hematoietic cells, such as hematopoietic progenitor cells and stem cells (HSCs).

Optimized vaccines to provide protection against ebola and other viruses

The invention is related to a nucleic acid molecule comprising a polynucleotide encoding a modified filovirus glycoprotein (GP) having at least one amino acid change located in a relatively conserved region of said GP that decreases in vitro cytotoxicity and retains immunogenicity when compared to in vitro cytotoxicity and immunogenicity of a wild type filovirus GP, and related modified filovirus GPs, plasmid DNAs, recombinant viruses, adenoviruses, pharmaceutical compositions, vaccine compositions, antibodies that are specifically reactive with the modified filovirus GPs, and related methods of making and using the same.

Proteinaceous particles containing retroviral element

A DNA construct comprising (a) a single promoter; (b) a gag-derived sequence from a complex retrovirus; (c) a rev-like element; (d) an RRE-like element; and (e) donor and acceptor elements; wherein (i) elements (a) to (e) are arranged in such a fashion that in the construct that the promoter is capable of driving expression of both the gag-derived sequence and, by virtue of the donor and acceptor elements, the rev-like element; (ii) the construct does not contain a functional env gene.

一种泡沫病毒包装载体系统及其构建方法和试剂盒

本申请涉及生物技术领域，尤其是涉及一种泡沫病毒包装载体系统及其构建方法和试剂盒。本申请采用五质粒法进行泡沫病毒包毒，获得感染能力明显增强、生产滴度明显增加的泡沫病毒包装载体系统。其中，本申请在优化的辅助质粒A、辅助质粒B、辅助质粒C的基础上(所述辅助质粒A的核苷酸序列如SEQ ID NO:1所示；所述辅助质粒B的核苷酸序列如SEQ ID NO:2所示；所述辅助质粒C的核苷酸序列如SEQ ID NO:3所示)，在泡沫病毒包装过程中额外加入外源糖蛋白质粒能够有效提高泡沫病毒侵染细胞效率，从而达到滴度的提升，并且还能降低生产成本的同时提高泡沫病毒的应用价值。