GENETIC ABOLISHMENT AND EXCHANGE

CATALYTIC SUBUNIT THE HUMAN TELOMERASE

PROCEDURE FOR THE PRODUCTION SYNTHETIC OLIGONUKLEOTIDE, SPECIFICALLY IN REGULATION PLACES ON DUPLEX DNA MOLECULES BINDING BY FORMS A KOLINEAREN OF A TRIPLEX, THE SYNTHETIC OLIGONUKLEOTIDE AND PROCEDURES FOR YOUR PRODUCTION.

MODULATION OF THE GENEXPRESSION BY INTERVENTION IN THE RNA SECONDARY STRUCTURE

CHEMICAL-MODIFIED OLIGONUKLEOTIDE FOR SITESPEZIFI MUTAGENESIS

USE OF MOB-5 IN PAIN

Mammalian telomerase

Treatment of androgen-associated baldness using antisense oligomers

Novel uses of triplex forming oligonucleotides for the treatment of human diseases

Human telomerase catalytic subunit

ENZYMATIC SYNTHESIS OF SSDNA

Methods and compositions for producing single-stranded cDNA (ss-cDNA) with a vector-based system in eukaryotic cells. The vector contains all necessary signaling instructions and enzymatic functions to allow the host cell to produce the ssDNA encoding a desired nucleic acid sequence (a "sequence of interest"). Described are the components included in the vector for synthesizing ssDNA in vivo. They include (1) a reverse transcriptase gene, (2) a genetic element that supplies the template for the desired ssDNA sequence of interest, and (3) a second genetic element located proximal to the genetic element encoding the sequence of interest that supplies the primer site for reverse transcription by the reverse transcriptase molecule. The vector also contains appropriate promoter(s)/enhancer(s). Also described herein is a method to construct a vector including these components.

CHIMERIC MOLECULES TO MODULATE GENE EXPRESSION

... ²²²The present invention provides a chimeric molecule including a base-pairing ²segment that binds specifically to a single-stranded nucleic acid molecule; ²and a moiety that modulates splicing or translation. The invention also ²provides a chimeric molecule including a base-pairing segment that binds ²specifically to a double-stranded nucleic acid molecule; and a peptide that ²modulates transcription, wherein the peptide comprises up to about one hundred ²amino acid residues.² ...

ANTISENSE OLIGONUCLEOTIDE CONSTRUCTS BASED ON .BETA.-ARABINOFURANOSE AND ITS ANALOGUES

The present invention relates to modified oligonucleotide therapeutic agents to selectively prevent gene transcription and expression in a sequence-specific manner. In particular, this invention relates to the selective inhibition of protein biosynthesis via antisense strategy using oligonucleotides constructed from arabinonucleotide or modified arabinonucleotide residues. More particularly this invention relates to the use of antisense oligonucleotides having arabinose sugars to hybridize to complementary RNA such as cellular messenger RNA, viral RNA, etc.

HUMAN TELOMERASE CATALYTIC SUBUNIT

The invention provides compositions and methods related to human telomeras e reverse transcriptase (hTRT), the catalytic protein subunit of human telomerase. The polynucleotides and polypeptides of the invention are useful for diagnosis, prognosis and treatment of human diseases, for changing the proliferative capacity of cell s and organisms, and for identification and screening of compounds and treatments useful for treatment of diseases such as cancers.

COMPOSITIONS AND METHODS FOR MODULATING GENE EXPRESSION

A description of novel artificial transcription factors (ATFs) is provided having a non- peptidic DNA-binding domain, flexible linker, and an effector domain based on a small molecule compound. These ATFs are capable of modulating transcription from nucleic acids both in vitro and in vivo. Importantly, these novel ATFs are capable of targeting and modulating the transcription of native (endogenous) genes in vivo. Method for targeted regulation of gene expression and the development of new class of pharmaceuticals are also provided.

OLIGOMERS WHICH INHIBIT THE EXPRESSION OF INTERLEUKIN GENES

Oligomers for inhibiting expression of interleukin genes are described. It is be lieved that each oligomer, when introduced into a cell, is capable of forming a transcription-inhibiting complex composed of the oligome r and an interleukin gene. The oligomer preferably binds in the antiparallel orientation to the polypurine strand of a polypurine-polypyr imidine region of the interleukin gene.

Catalytic subunit of human Telomerase.

Pure and recombinant human Telomerase Reverse Transcriptase and its variants

A pure or recombinant protein preparation (I) of human telomerase reverse transcriptase (hTRT), a ribonucleoprotein, or its variants are new.- Also claimed are: - (1) isolated, synthetic, pure or recombinant polynucleotides that encode (I); - (2) use of polynucleotide (II) (10 nucleotide to 10 kb) that has contiguous sequences complementary to naturally occuring hTRT gene or mRNA, in screening of the gene or mRNA or to prepare a recombinant host cell; - (3) a cell containing (II); and - (4) an antibody against hTRT.- The following methods are also claimed: - (A) determining whether a test compound is a modulator of hTRT, by detecting the change in hTRT recombinant protein or polynucleotide, on administration of the compound; - (B) preparation of recombinant telomerase by contacting (I) with a telomerase RNA component; - (C) detection of the hTRT RNA or protein in a sample by binding a relevant probe to the sample and detecting the complex formed or in the case of RNA detection, amplifying ...

ANTI-SENSE OLIGONUCLEOTIDES FOR TREATING CONGENITAL AMAVROZALEBERA

NOVEL TYROSINASE-SPECIFIC ANTIGENIC OLIGONUCLEOTIDES AS DEPIGMENTING AGENTS

The invention concerns an antigenic oilgonucleotide hybridizing specifically with the gene encoding human tyrosinase through Hoogsteen pairing between complementary bases, said oligonucleotide forming a triple-helix structure with the human tyrosinase gene. The invention also concerns the use of said oligonucleotide as depigmenting or skin-whitening agent in a cosmetic composition or in a dermatological composition. © KIPO & WIPO 2008 ...

Isolated proteìnica preparation and of htrt, I break up of proteìna of htrt, telomerase human being, isolated polinucleotìdeo, vector of expression, cell, isolated not human organism, antocorpo or recombinant, processes to determine if a composition or treatment are a modulator of an activity or expression of htrt, if a made up of test is a modulator of an activity of transcriptase reversa of telomerase, to identify a composition that modulates the activity of htrt, to prepare telomerase recombinant, to detect a product of people of htrt in a sample and the presence of for menosuma cell positive human being of telomerase in a biological sample, to diagnosis a condition related telomerase in a patient and cancer to supply a prognostic a cancer patient, to monitor the capacity of a treatment anti-cancer, to reduce the proliferativa capacity of the cancerìgenas cells in a patient, to increase the proliferativa capacity of a vertebrate cell, to inside deal with a condition associated with one nìvel raised activity of telomerase of a cell, to isolate an acid selected nucleico of unknown sequência, to detect a product of the gene of htrt in a sample and the presence of at least a cell positive human being of telomerase in a biological sample, kit for the detention of a gene or product of the gene of htrt, compositions farmacológica and pharmaceutical, isolated vaccine, proteìna htrt, uses of a polinucleotìdeo, antibody and of an agent of increase of the expression of htrt, proteìna, variant or I break up, and, use of one proteìna, polipeptìdeo or break up use of the same ones.

COMPOSITIONS AND METHODS FOR TARGETED INACTIVATION OF HIV CELL SURFACE RECEPTORS

Compositions for targeted mutagenesis of cell surface receptors for HIV and methods of their use are provided herein. The compositions include triplex-forming molecules that displace the polypyrimidine strand of target duplex and form a triple-stranded structure and hybrid duplex in a sequence specific manner with the polypurine strand of the target duplex. The triplex-forming molecules include a mixed-sequence "tail" which increases the stringency of binding to the target duplex, improves the frequency of modification at the target site, and reduces the requirement for a polypurine :polypyrimidine stretch. Methods for using the triplex-forming molecules in combination with one or more donor oligonucleotides for targeted modification of sites within or adjacent to genes that encodes cell surface receptors for human immunodeficiency virus (HIV) are also disclosed. Methods for ex vivo and in vivo prophylaxis and therapy of HIV infection using the disclosed compositions are also provided.

NOVEL TYROSINASE-SPECIFIC ANTIGENIC OLIGONUCLEOTIDES AS DEPIGMENTING AGENTS

The invention concerns an antigenic oilgonucleotide hybridizing specifically with the gene encoding human tyrosinase through Hoogsteen pairing between complementary bases, said oligonucleotide forming a triple-helix structure with the human tyrosinase gene. The invention also concerns the use of said oligonucleotide as depigmenting or skin-whitening agent in a cosmetic composition or in a dermatological composition.

SYSTEM FOR REGULATING IN VIVO THE EXPRESSION OF A TRANSGENE BY CONDITIONAL INHIBITION

The invention concerns novel constructs, compositions and a novel method for regulating in vivo the expression of a transgene of interest by conditional inhibition, and their uses for experimental, clinical and therapeutic purposes or for producing animals or plants. More particularly, the novel regulating method consists in the co-expression of a transgene of interest coding for a transcript of interest and an inhibitor transgene coding for an inhibitor transcript specific of the transcript of interest, so as to obtain constitutive inhibition of the activity of the transcript of interest, and so as to be able to ensure an efficient regulation of the transcript of interest, either by inhibiting its inhibitor transcript, or by activating the transcript of interest, or still by activating the transcript of interest and simultaneous inhibiting of its inhibitor transcript.

CELL GROWTH REGULATORY GENES

Transcriptionally regulated growth-response genes play a pivotal role in the determination o a cell's fate. p53 is known to transcriptionally regulate genes important in regulating cell growth potential. Using differential RT-PCR analysis of rat embryo fibroblast cells containing a temperature-sensitive p53 allele, we were able to isolate several transcripts upregulated specifically in cells harboring the wild-type p53 protein. Two of these genes, SM20 and microsomal epoxide hydrolase (mEH), are previously described genes. Two previously uncharacterized cDNA's, cell growth regulatory (CGR) genes CGR11 and CGR19, were isolated. The predicted amino acid sequences of these novel proteins contain known motifs; EF-hand domains (CGR11) and a ring-finger domain (CGR19), are suggestive of function. CGR11 and CGR19 appear to be primary response genes expressed at 0.05 % and 0.01 % of the total mRNA in wild-type p53 cells. Both CGR11 and CGR19 as well as SM20 and mEH, are able to inhibit growth of ...

TARGETED MODIFICATION OF THE CCR-5 GENE

Modified oligonucleotides, capable of forming triple-stranded complexes with the CCR-5 chemokine receptor gene, are provided. The oligonucleotides bear cross-linking groups, capable of causing targeted modification of the CCR-5 gene. Such modifications can impair the ability of the CCR-5 gene product to serve as a co-receptor for human immunodeficiency viruses.

Texaphyrins and uses thereof

A texaphyrin having substituents containing ethoxy groups, methods for using texaphyrins in photodynamic therapy, and cleavage of a polymer of deoxyribonucleic acid are disclosed. The in vivo treatment of tumors and atheroma is demonstrated using Lu(III)texaphyrin complexes. A preferred method of use is the site-specific cleavage of a polymer of deoxyribonucleic acid and a preferred texaphyrin is a derivatized texaphyrin having binding specificity, in particular, a texaphyrin covalently coupled to a site-directing molecule, preferably an oligonucleotide.

TARGETING GENE AMPLIFICATION IN CANCER USING TRIPLEX FORMATION AS A THERAPEUTIC STRATEGY

Disclosed herein are methods and agents for the treatment of cancer using p53-independent apoptosis to reduce the number of p53-depleted or p53-mutated cancer cells that have amplified HER2 gene. Also disclosed herein are methods and agents for the treatment of HJ-R2-positive: cancer in individuals with Li-Fraumeni Syndrome.

NOVEL PEPTIDE NUCLEIC ACIDS

A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker.

HYDROLYSIS AND PHOTOCLEAVAGE OF NUCLEIC ACID USING A METAL COMPLEX

СТАБИЛЬНОЕ И СЕЛЕКТИВНОЕ ОБРАЗОВАНИЕ ТРИПЛЕКСОВ И ДУПЛЕКСОВ ХУГСТЕНОВСКОГО ТИПА С ПРИМЕНЕНИЕМ СКРУЧЕННЫХ ИНТЕРКАЛИРУЮЩИХ НУКЛЕИНОВЫХ КИСЛОТ (TINA) И СПОСОБ ПОЛУЧЕНИЯ TINA

Изобретение относится к области биохимии и молекулярной биологии и может быть использовано для детекции нуклеиновых кислот, диагностики и/или лечения заболеваний. Гибкий мономер, увеличивающий стэкинг оснований, содержит скелетную мономерную единицу олигонуклеотида или олигонуклеотидного аналога, которая с помощью алкилендиола и линкера соединена с двумя циклическими кольцевыми системами. Кольцевые системы связаны между собой посредством конъюгатора. Гибкий мономер может быть адаптирован для встраивания в олигонуклеотид. Способ получения олигонуклеотида предусматривает в течение олигонуклеотидного синтеза встраивание гибкого мономера, увеличивающего стэкинг оснований и адаптированного для встраивания в олигонуклеотид. Олигонуклеотид может содержать один или более гибких мономеров, увеличивающих стэкинг оснований. 4 н. и 8 з.п. ф-лы, 6 ил., 4 табл., 10 пр.

HYDROLYSIS AND PHOTOFISSION OF NUCLEIC ACID USING METAL COMPLEXES

STRATEGY TO UNTERDRUCKUNG THE EXPRESSION OF AN ENDOGENOUS GENE BY USE OF CONNECTIONS, TO THE NON--CODING REGIONS OF THE RESTRAINING GENE BINDING ABILITY

ALLELE DISMANTLING

MAMMAL TELOMERASE ONE

ON BETA ARABINOSE ONES, AND ITS SIMILAR ONES, BASED ANTI-SCYTHE OLIGONUKLEOTIDE

NON--BACTERIAL KLONIERUNGSSYSTEM FOR ADMINISTRATION AND EXPRESSION OF NUCLEIC ACIDS

Liver-specific inducible promoters and methods of use thereof

The present invention relates to inducible regulatory elements, promoters and vectors, especially gene therapy vectors, and methods of their use.

Formation of triple helix complexes of double stranded DNA using nucleoside oligomers which comprise purine base analogs

Chimeric molecules to modulate gene expression

Synthetic triple helix-forming compounds

Vectors for transferring nucleic acids, compositions containing them and their uses

Hydrolysis and photocleavage of nucleic acid using a metal complex

Delivery of Oligonucleotide-Functionalized Nanoparticles

The present invention relates to compositions and methods for delivering an oligonucleotide functionalized nanoparticle.

Chimeric double-stranded nucleic acid

Disclosed are double-stranded nucleic acid complexes that suppress the expression of a target gene by means of an antisense effect, and methods for using the same. One method for reducing the level of a transcription product in a cell comprises contacting with the cell a composition comprising: a double-stranded nucleic acid complex comprising a first nucleic acid strand annealed to a second nucleic acid strand, wherein: the first nucleic acid strand (i) comprises nucleotides and optionally nucleotide analogs, and the total number of nucleotides and nucleotide analogs in the first nucleic acid strand is from 8 to 100, (ii) comprises at least 4 consecutive nucleotides that are recognized by RNase H when the first nucleic acid strand is hybridized to the transcription product, and (iii) the first nucleic acid strand hybridizes to the transcription product; and the second nucleic acid strand comprises nucleotides and optionally nucleotide analogs.

COMPOUNDS AND THEIR USE FOR SPECIFIC AND SIMULTANEOUS INHIBITION OF GENES INVOLVED IN DISEASES AND RELATED DRUGS

The invention relate to the use of a compound of formula A-B-C Wherein A is a DNA sequence-specific ligand capable of simultaneously and specifically recognizing a sequence common to genes of pathological interest; B is a linker arm, said linker arm being bound to the 3' end of A; C is a topoisomerase I posion; for the preparation of a drug for the treatment of a disease brought about by the expression of a gene and said gene is inhibited by the stabilized topoisomerase I-mediated DNA cleavage. Application, particularly, for the treatment of infective microorganism or virus, dismetabolic disease and autoimmune disease.

INTERLEUKIN-22 POLYPEPTIDES, NUCLEIC ACIDS ENCODING THE SAME AND METHODS FOR THE TREATMENT OF PANCREATIC DISORDERS

The present invention is directed to interleukin-22 polypeptides and nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention.

PRODUCTION OF STABLE NON-POLYADENYLATED RNAS

The invention relates in aspects to hybrid RNAs lacking a poly-A tail and nucleic acid vectors for expressing the RNA. The hybrid RNAs in some instances have a 3' terminal stabilizing triple helical structure. Related methods for expressing said RNAs in vivo and in vitro are also disclosed.

NON-BACTERIAL CLONING IN DELIVERY AND EXPRESSION OF NUCLEIC ACIDS

Novel double-stranded DNAs, expression vectors and methods for their use are provided in which the intracellular expression of the double-stranded DNAs alters the phenotype of a cell to determine the function of a gene of interest. The double-stranded DNAs encode a family of catalytic RNAs targeted to the mRNA of a gene of interest. Cleavage of the mRNA results in an altered cell phenotype from which the function of the product encoded by the mRNA is determined. The compositions find use in high-throughput screens to assign gene functions which eliminate the requirement of bacterial cloning.

METHOD FOR SYNTHESIZING SINGLE-STRANDED STEM-LOOP DNAS, THE PRODUCTS AND USES THEREFOR

A method of synthesis of new and useful single-stranded DNAs which have a stem-loop configuration (ss-slDNA). The method is an in vivo or an in vitro synthesis. Replicating vehicles which produce these ss-slDNAs . The ss-slDNAs are described. Uses for these slDNAs are disclosed. They can be used for introducingrandom mutations, they lend themselves for replication by a variant of the PCR method. Other uses are disclosed.

NOVEL PEPTIDE NUCLEIC ACIDS

A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker.

ANTISENSE AND TRIPLEX THERAPEUTIC AGENTS AND METHODS

Antisense and anti-gene oligonucleotides and modified oligonucleotides with plural intercalating molecules attached for use in antisense and triplex therapy. Virally infected blood, blood plasma or serum samples are rendered significantly less infectious while maintaining the integrity of the sample for clinical analysis. Synthetic strands of oligonucleotides, and/or nucleaseresistant derivatives of oligonucleotides having intercalating agent molecules attached thereto provide an additive for incorporation into a blood sample which is to undergo analytical tests and procedures. Sterilization of a significant number of intracellular target viruses in the sample renders the sample significantly less capable of infecting those handling it. An appropriate binding material additive, such as an antibody or aptamer, which is specific for epitopes or other binding sites on the free or extracellular target virus, may also be used, either alone or in combination with the intracellular strand ingredients ...

OLIGOMERS WHICH INHIBIT EXPRESSION OF COLLAGEN GENES

Oligomers which inhibit expression of a collagen gene are described. It is believed that each oligomer, when introduced into a cell, forms a transcription-inhibiting complex composed of the oligomer and the collagen gene promoter region. The oligomer, preferably a phosphorothioate deoxyoligonucleotide, preferably binds in the antiparallel orientation to the polypurine strand of a polypurine-polypyrimidine region of the promoter region of a mammalian .alpha.1(I) collagen gene.

GENETIC SUPPRESSION AND REPLACEMENT

A strategy for suppressing specifically or partially specifically an endogenous gene and introducing a replacement gene, said strategy comprising the steps of: 1) providing suppressing nucleic acids or other suppression effectors able to bind to an endogenous gene, gene transcript or gene product to be suppressed, and 2) providing genomic DNA or cDNA (complete or partial) encoding a replacement gene wherein the suppressing nucleic acids are unable to bind to equivalent regions in the genomic DNA or cDNA to prevent expression of the replacement gene. The replacement nucleic acids have modifications in one or more third base (wobble) positions such that replacement nucleic acids still code for the wild type or equivalent amino acids.

PROMOTER FOR TELOMERASE REVERSE TRANSCRIPTASE

The invention provides compositions and methods related to human telomerase reverse transcriptase (hTRT), the catalytic protein subunit of human telomerase. The polynucleotides and polypeptides of the invention are useful for diagnosis, prognosis and treatment of human diseases, for changing the proliferative capacity of cells and organisms, and for identification and screening of compounds and treatments useful for treatment of diseases such as cancers.

TELOMERAZA REVERSE TRINSKRIPTAZA

NEW OLIGONUCLEOTIDES AND USE Of OLIGONUCLEOTIDES INTERACTING WITH GENE CODING FOR TYROSINASE RELATED PROTEIN-1 (TRP-1) TO MODULATE ITS EXPRESSION LIKE AGENTS DEPIGMENTANTS of IT.

METHODS AND COMPOSITIONS FOR TREATING CANCER

The present invention relates to methods and compositions for treating cancers by reducing the expression or activity of one or more of the genes encoding protein kinases ATR, MAST2, MAP3K6, TBKl, ADRBK2, CDKL2, LATS2, STK32B, STKIl, DDRl3 PSKH2, and NEK8, and/or the encoded kinases. The invention also relates to methods and compositions for determining the responsiveness of a cancer patient to anti-cancer drugs based on the status of one or more of such kinases. The invention further relates to methods and compositions for screening compounds that can be used to modulate the expression/activity of these kinases.

METHODS FOR REGULATION OF P53 TRANSLATION AND FUNCTION

The present invention relates to novel methods for modulating the activity of p53 tumor suppressor protein by affecting p53 translational regulation. More specifically, the invention relates to novel methods for modulating p53 mRNA translation in a cell by affecting a function of a p53 5'-untranslated region (5'UTR), including its interaction with proteins such as Ribosomal Protein L26 (RPL26), nucleolin, and p53. The invention also relates to the use of these methods for treating cancer, neurodegenerative disorders and minimizing the negative effects of cellular stresses.

STRATEGY FOR SUPPRESSING THE EXPRESSION OF AN ENDOGENEOUS GENE BY USING COMPOUNDS THAT ARE ABLE TO BIND TO THE NON-CODING REGIONS OF THE GENE TO BE SUPPRESSED

The invention provides strategy for suppressing expression of an endogenous gene, wherein said strategy comprises providing suppression effectors able to bind to the non-coding regions of a gene to be suppressed, to prevent the functional expression thereof. The suppression effectors may be antisense nucleic acids, and the non-coding regions can include the transcribed but non-translated regions of a gene. The strategy can also introduce a replacement gene.

METHOD FOR CIRCULARIZING OLIGONUCLEOTIDES AROUND A DOUBLE STRANDED NUCLEIC ACID, RESULTING STRUCTURES AND USES THEREOF

Le procédé de circularisation d'un oligonucléotide selon l'invention comprend: l'incubation d'un acide nucléique double brin comprenant une séquence cible, avec un oligonucléotide simple brin comprenant une partie centrale capable de se fixer sur ladite séquence cible, reliée par des séquences espaceurs à des séquences terminales en 5' et 3', ces séquences étant: soit a) complémentaires de la séquence d'une matrice oligonucléotidique; soit x) partiellement complémentaires l'une de l'autre, de manière à pouvoir s'hybrider l'une à l'autre en formant un double brin tout en conservant une extrémité en simple brin, laquelle est capable de s'hybrider à la séquence terminale d'un autre oligonucléotide, dit oligonucléotide-boucle, qui possède une structure en épingle à cheveux, avec une partie en simple brin et une partie repliée qui forme un double brin, la mise en contact, dans le premier cas a), du complexe formé avec ladite matrice oligonucléotidique, dans des conditions permettant l'hybridation ...

ANTISENSE OLIGOMERS FOR INHIBITING HUMAN PAPILLOMAVIRUSES

Antisense oligomers complementary to and capable of hybridizing to a target region of an mRNA or pre-mRNA of a human papillomavirus are provided. Suitable target regions include sequences selected from a translation initiation codon, a splice donor site, a splice acceptor site, a coding region, a polyadenylation signal, a 3'-untranslated region or a 5'-untranslated region of an HPV gene.

Human telomerase catalytic subunit

The invention provides compositions and methods related to human telomerase reverse transcriptase (hTRT), the catalytic protein subunit of human telomerase. The polynucleotides and polypeptides of the invention are useful for diagnosis, prognosis and treatment of human diseases, for changing the proliferative capacity of cells and organisms, and for identification and screening of compounds and treatments useful for treatment of diseases such as cancers.

Oligonucleotides with inverted polarity

Oligonucleotides having tandem sequences of inverted polarity, i.e., oligonucleotides comprising regions of the formula: 3' - - - - - 5' - - C - - 5' - - - - - 3' (1) or 5' - - - - - 3' - - C - - 3' - - - - - 5' (2) wherein -C- symbolizes any method of coupling the nucleotide sequence of opposite polarity, are useful for forming an extended triple helix with a double-helical nucleotide duplex. The inverted polarity also stabilizes the single-strand oligonucleotides to exonuclease degradation.

Texaphyrins and uses thereof

A texaphyrin having substituents containing ethoxy groups, methods for using texaphyrins in photodynamic therapy, and cleavage of a polymer of deoxyribonucleic acid are disclosed. The in vivo treatment of tumors and atheroma is demonstrated using Lu(III)texaphyrin complexes. A preferred method of use is the site-specific cleavage of a polymer of deoxyribonucleic acid and a preferred texaphyrin is a derivatized texaphyrin having binding specificity, in particular, a texaphyrin covalently coupled to a site-directing molecule, preferably an oligonucleotide.

Method for synthesizing single-stranded stem-loop DNA's the products and uses therefore

A method of synthesis of new and useful single-stranded DNAs which have a stem-loop configuration (ss-slDNA). The method is an in vivo or an in vitro synthesis. Replicating vehicles which produce these ss-slDNAs. The ss-slDNAs are described. Uses for these slDNAs are disclosed. They can be used for introducing random mutations, they lend themselves for replication by a variant of the PCR method. They can also be used for regulating gene function. Other uses are disclosed.

Treating cancer using antisense oligonucleotides against telomerase reverse transcriptase

This disclosure provides TRT antisense oligonucleotides, methods of detecting TRT, methods of diagnosing telomerase-related conditions, methods of diagnosing and providing a prognosis for cancer, and methods of treating telomerase-related conditions, including cancer.

АПТАМЕРЫ, СОДЕРЖАЩИЕ ПОСЛЕДОВАТЕЛЬНОСТИ НУКЛЕИНОВЫХ КИСЛОТ ИЛИ АНАЛОГОВ НУКЛЕИНОВЫХ КИСЛОТ, СВЯЗАННЫЕ ГОМОЛОГИЧНО, ИЛИ В НОВЫХ КОМПЛЕКСАХ

... 1. Способ связывания лиганда, предусматривающий: обеспечение аптамера, содержащего, по меньшей мере, две параллельные или антипараллельные гетерополимерные содержащие нуклеиновые основания последовательности, связанные вместе взаимодействием комплементарных оснований по Уотсону-Крику или взаимодействием гомологичных оснований, где: (а) где указанный аптамер содержит дуплекс и указанные, по меньшей мере, две последовательности связаны вместе взаимодействием комплементарных оснований по Уотсону-Крику с параллельной направленностью, (b) указанный аптамер содержит дуплекс и указанные, по меньшей мере, две последовательности связаны вместе взаимодействием гомологичных оснований с параллельной или антипараллельной направленностью; (с) указанный аптамер содержит триплекс и указанные, по меньшей мере, две последовательности связаны вместе взаимодействием комплементарных оснований по Уотсону-Крику с параллельной или антипараллельной направленностью; (d) указанный аптамер содержит триплекс и указанные ...

Human telomerase reverse transcriptase promoter

Human telomerase catalytic subunit

LINKED PEPTID NUCLEIC ACIDS

STRUCTURE OF HIGHER ORDER AND CONNECTION OF PEPTIDNUKLEINSÄUREN

MORE HUMANLY TELOMERASE REVERSE TRANSCRIPTASE OF PROMOTER

CHIMÄRE MOLECULES FOR THE MODULATION OF THE GENEXPRESSION

INTRACELLULAR GENERATION OF SINGLE-STRANDED DNA

Antisense oligonucleotide generators

Antisense oligonucleotides for the treatment of Leber congenital amaurosis

The present invention relates to the fields of medicine and immunology. In particular, it relates to novel antisense oligonucleotides that may be used in the treatment, prevention and/or delay of Leber congenital amaurosis.

DNA photocleavage using texaphyrins

Antisense oligomers for inhibiting human papillomaviruses

Oligomers which inhibit the expression of interleukin genes

TRIPLE STRANDED NUCLEIC ACID AND METHODS OF USE

INTERLEUKIN-22 POLYPEPTIDES, NUCLEIC ACIDS ENCODING THE SAME AND METHODS FOR THE TREATMENT OF PANCREATIC DISORDERS

The present invention is directed to interleukin-22 polypeptides and nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention.

HUMAN TELOMERASE REVERSE TRANSCRIPTASE

The invention provides compositions and methods related to human telomerase reverse transcriptase (hTRT), the catalytic protein subunit of human telomerase. The polynucleotides and polypeptides of the invention are useful for diagnosis, prognosis and treatment of human diseases, for changing the proliferative capacity of cells and organisms, and for identification and screening of compounds and treatments useful for treatment of diseases such as cancers.

TRIPLE HELIX FORMATION IN OLIGONUCLEOTIDE THERAPY

Oligonucleotides having tandem sequences of inverted polarity, i.e., oligonucleotides comprising regions of the formula: 3'-----5'--C--5'-----3' or 5'-----3'--C--3'-----5', wherein -C- symbolizes any method of coupling the nucleotide sequence of opposite polarity, are useful for forming an extended triple helix with a doublehelical nucleotide duplex. Single or mixed motif oligomers may be used. The inverted polarity also stabilizes the single-strand oligonucleotides to exonuclease degradation.

OVER EXPRESSION OF SINGLE-STRANDED MOLECULES

... 2118518 9420639 PCTABS00033 A method of synthesis of new and useful single-stranded DNAs which have a stem-loop configuration (ss-slDNA). The method is an $i (in vivo) or an in vitro synthesis. Replicating vehicles which produce these ss-slDNAs. The ss-slDNAs are described. Uses for these slDNAs are disclosed. They can be used for introducing random mutations, they lend themselves for replication by a variant of the PCR method. They can also be used for regulating gene function. Other uses are disclosed.

MAMMALIAN TELOMERASE

Nucleic acids comprising the RNA component of a mammalian telomerase are useful as pharmaceutical, therapeutic, and diagnostic reagents.

MAMMALIAN TELOMERASE

Nucleic acids comprising the RNA component of a mammalian telomerase are useful as pharmaceutical, therapeutic, and diagnostic reagents.

GENETIC SUPPRESSION AND REPLACEMENT

A strategy for suppressing specifically or partially specifically an endogenous gene and introducing a replacement gene, said strategy comprising the steps of: 1) providing suppressing nucleic acids or other suppression effectors able to bind to an endogenous gene, gene transcript or gene product to be suppressed, and 2) providing genomic DNA or cDNA (complete or partial) encoding a replacement gene wherein the suppressing nucleic acids are unable to bind to equivalent regio ns in the genomic DNA or cDNA to prevent expression of the replacement gene. The replacement nucleic acids have modifications in one or more third base (wobble) positions such that replacement nucleic acids still code for the wild type or equivalent amino acids. ...

INHIBITION OF PROLIFERATION OF CELLS

The present invention provides a method of inhibiting proliferation of cells. The method comprises inhibiting induction or decreasing expression of Egr-1 or decreasing the nuclear accumulation or activity of the Egr-1 gene product. The present invention also provides a method of reducing the incidence of restenosis in subject. The method comprises administering to the subject an agent which inhibits induction or decreases expression of Egr-1 or decreases the nuclear accumulation or activity of the Egr-1 gene product.

New anti-gene oligonucleotide comprising nucleotide sequence, is tyrosinase related protein-1 gene expression inhibitor, useful to treat/prevent e.g. diseases resulting in the over expression and hyperactivity of the tyrosinase

La présente invention concerne un oligonucléotide anti-gène s'hybridant spécifiquement avec le gène codant pour la tyrosinase related protein-1 humaine par appariement Hoogsteen entre les bases complémentaires, ledit oligonucléotide formant une structure en triple hélice avec le gène de la tyrosinase related protein-1 humaine. L'invention concerne également l'utilisation dudit oligonucléotide comme agent dépigmentant ou blanchissant de la peau dans une composition cosmétique ou dans une composition dermatologique.

Regulating expression of transgenes in plants and animals, useful e.g. for gene therapy, comprises cotransfection with a transgene and a sequence that expresses an inhibitory transcript

La présente invention concerne de nouvelles constructions, compositions et un nouveau procédé pour la régulation de l'expression d'un transgène d'intérêt in vivo par inhibition conditionnelle, ainsi que leurs utilisations dans les domaines expérimentaux, cliniques, thérapeutiques, ou pour la production d'animaux ou végétaux. Plus particulièrement, le nouveau procédé de régulation repose sur la coexpression d'un transgène d'intérêt codant pour un transcrit d'intérêt et d'un transgène inhibiteur codant pour un transcrit inhibiteur spécifique du transcrit d'intérêt, de sorte à obtenir une inhibition constitutive de l'activité du transcrit d'intérêt, et à pouvoir assurer une régulation efficace du transcrit d'intérêt, soit par inhibition de son transcrit inhibiteur, soit par activation du transcrit d'intérêt, soit encore par activation du transcrit d'intérêt et inhibition concomitante de son transcrit inhibiteur.

COMPOSE Of NUCLEIC ACIDS OF PROTEIN AND POLYNUCLEOTI OF CODING FOR the CATALYTIC SUB-UNIT OF TELOMERASE HUMAI, PRODUCTION AND APPLICATIONS

Dans le domaine du génie génétique, l'invention concerne des séquences d'amino acides liées à la transcriptase reverse de télomérase humaine, qui est une sous-unité de protéine catalytique de télomérase humaine. Ces polynucléotides et polypeptides peuvent servir à produire des compositions pour le diagnostic, le pronostic et le traitement de maladies humaines, pour modifier la capacité de prolifération de cellules, et pour identifier et rechercher des composés et traitements utiles dans le domaine médical. Exemples d'application: recherche et dépistage de cancers et d'altérations dues au vieillissement.

OSTEOARTHRITIS BIOMARKERS AND USES THEREOF

The invention relates to the identification and selection of novel biomarkers and the identification and selection of novel biomarker combinations which are differentially expressed in osteoarthritis and/or in a particular stage of 6steoarthritis, as well as a means of selecting the novel biomarker combinations. The measurement of expression of the products of the biomarkers and combinations of biomarkers of the invention demonstrates particular advantage in one or more of the following: (a) diagnosing individuals as having arthritis, (b) differentiating between two stages of osteoarthritis (OA) and (c) diagnosing individuals as having a particular stage of osteoarthritis (OA). As would be understood, in order to measure the products of biomarkers of the invention, polynucleotides and proteins which specifically and/or selectively hybridize to the products of the biomarkers of the invention are also encompassed within the scope of the invention as are kits containing said polynucleotides ...

HYBRIDIZATION-STABILIZING CONSTRUCT

A Z-shaped construct having the capacity to hybridize to double stranded DNA in a trans fashion to affect transcription is produced from at least two oligonucleotides, connected to each other, wherein the oligonucleotides are connected to one another through one of sequence specific Watson-Crick base pairing; a covalent linker or a covalent bond directly between the backbones or the bases of said oligonucleotides; or a non-covalent linker or a non-covalent bond directly between the backbones or the bases of said oligonucleotides.

Method for synthesizing single-stranded stem-loop DNA's the products and uses therefore

A method of synthesis of new and useful single-stranded DNAs which have a stem-loop configuration (ss-slDNA). The method is an in vivo or an in vitro synthesis. Replicating vehicles which produce these ss-slDNAs. The ss-slDNAs are described. Uses for these slDNAs are disclosed. They can be used for introducing random mutations, they lend themselves for replication by a variant of the PCR method. They can also be used for regulating gene function. Other uses are disclosed.

Methods and compositions for triple helix formation

Improved oligonucleotides and processes for their use for specific recognition of a target sequence in double-stranded nucleic acid through the formation of an alternate strand triple-helix. The triple-helix forming oligonucleotides bind in a parallel and antiparallel orientation, respectively, to target sequences on alternate strands of the double helical nucleic acid. The oligonucleotides are useful as diagnostic or therapeutic agents and can incorporate an appropriate moiety in one or more nucleotides in the triple-helix forming oligonucleotide.

Genetic suppression and replacement

Methods and agents for suppressing expression of a mutant allele of a gene and providing a replacement nucleic acid are provided. The methods of the invention provide suppression effectors such as, for example, antisense nucleic acids, ribozymes, or RNAi, that bind to the gene or its RNA. The invention further provides for the introduction of a replacement nucleic acid with modified sequences such that the replacement nucleic acid is protected from suppression by the suppression effector. The replacement nucleic acid is modified at degenerate wobble positions in the target region of the suppression effector and thereby is not suppressed by the suppression effector. In addition, by altering wobble positions, the replacement nucleic acid can still encode a wild type gene product. The invention has the advantage that the same suppression strategy could be used to suppress, in principle, many mutations in a gene. Also disclosed is a transgenic mouse that expresses human rhodopsin (modified ...

Control of gene expression using a complex of an oligonucleotide and a regulatory peptide

A method for suppressing the expression of a selected gene in a cell the method comprising introducing into the cell a molecule comprising (1) a nucleic acid binding portion which binds to a site or associated with the selected gene which site is present in a genome and (2) an expression repressor portion, wherein the nucleic acid binding portion comprises an oligonucleotide or oligonucleotide mimic or analogue, and wherein the repressor portion comprises a polypeptide or peptidomimetic. Molecules for use in the methods of the invention are provided. The repressor may be a portion of a histone deacetylase or DNA methylase or polypeptide capable of recruiting a histone deacetylase or DNA methylase.

Novel inhibitors of retroviral reverse transcriptace

Disclosed are nucleic acid molecules, and methods of their use, which have a specific structure including a double helical domain and a G-quadruplex domain physically connected by a linker domain which may be nucleosidic or non-nucleosidic. These aptamers demonstrate potent inhibition of phylogenetically diverse primate lentiviral reverse transcriptases, which effect is largely independent of aptamer sequence provided that the aptamer has the specified structure.

Control of Gene Expression Using a Complex of an Oligonucleotide and a Regulatory Peptide

A method for suppressing the expression of a selected gene in a cell, the method comprising introducing into the cell a molecule comprising (1) a nucleic acid binding portion which binds to a site or associated with the selected gene which site is present in a genome and (2) an expression repressor portion, wherein the nucleic acid binding portion comprises an oligonucleotide or oligonucleotide mimic or analogue, and wherein the repressor portion comprises a polypeptide or peptidomimetic. Molecules for use in the methods of the invention are provided. The repressor may be a portion of a histone deacetylase or DNA methylase or polypeptide capable of recruiting a histone deacetylase or DNA methylase.

Sequence specific double-stranded dna/rna binding compounds and uses thereof

The present invention provides specific double-stranded DNA/RNA binding compounds having a polymeric structure, which are in fact, triplex forming molecules capable of binding tightly and specifically to predetermined sequences in the major groove of double stranded nucleic acid molecules; as well as pharmaceutical compositions comprising thereof. The triplex forming molecules and the pharmaceutical compositions of the invention can be used for various therapeutic applications such as site-specific modulation of gene expression, targeting of DNA or RNA damage, and gene knockout, as well as for diagnostic applications in vitro.

Chimeric molecules to modulate gene expression

The present invention provides a chimeric molecule including a base-pairing segment that binds specifically to a single-stranded nucleic acid molecule; and a moiety that modulates splicing or translation. The invention also provides a chimeric molecule including a base-pairing segment that binds specifically to a double-stranded nucleic acid molecule; and a peptide that modulates transcription, wherein the peptide comprises up to about one hundred amino acid residues.

cGAP-PNA MULTIVALENT PEPTIDE NUCLEIC ACID LIGAND DISPLAY

Described herein are compositions composed of peptide nucleic acid strands. In some aspects the peptide nucleic acid strands are complementary to at least a portion of another peptide nucleic acid strand that may have one or more gamma substituents, where the ratio of PNA strands is least 1:1. Certain gamma substituents are capable of effecting attachment of a PNA strand to a cell. The disclosure also concerns construction of nanostructure platforms and vaccines and use of the inventive compositions in inhibiting disease states in mammals. 1. A macromolecule comprising a plurality of linked peptide nucleic acid (PNA) strands , wherein each of said strands is independently composed of a plurality of nucleobase subunits , and each PNA strand is covalently linked to at least one other PNA strand via an amino acid linker , wherein the amino acid linker is a biological amino acid linker or a N ,N-dimethyl-lysine linker.2. The macromolecule of claim 1 , wherein the linked PNA strands form a linear arrangement claim 1 , a nonlinear arrangement claim 1 , or a branched arrangement.34.-. (canceled)5. The macromolecule of claim 1 , wherein at least one amino acid linker mediates the linkage of more than two PNA strands.6. The macromolecule of claim 1 , wherein the linked PNA strands each independently comprise from 2 to about 50 nucleobase subunits.7. (canceled)8. The macromolecule of claim 1 , wherein all of the linked PNA strands are of uniform length.9. The macromolecule of claim 1 , wherein at least one of the linked PNA strands differs in length from at least one other PNA strand.10. The macromolecule of claim 1 , wherein at least some of the linked PNA strands are individually bound to at least one complementary PNA strand to form a double stranded PNA segment.11. The macromolecule of claim 10 , wherein the ratio of linked PNA strands to complementary PNA strands isfrom about 2:1 to about 10:1,1213.-. (canceled)14. The macromolecule of claim 10 , wherein at least one ...

COMPOSITIONS AND METHODS FOR NEXT GENERATION SEQUENCING

Provided herein are compositions and methods for next generation sequencing using universal polynucleotide adapters. Further provided are universal adapters using locked nucleic acids or bridged nucleic acids. Further provided are barcoded primers of reduced length for extension of universal adapters. Further provided herein are universal adapter blockers. 1. A polynucleotide , wherein the polynucleotide comprises:a first strand, wherein the first strand comprises a first terminal adapter region, a first non-complementary region, and a first yoke region;a second strand, wherein the second strand comprises a second terminal adapter region, a second non-complementary region, and a second yoke region;wherein the first yoke region and the second yoke region are complementary, wherein the first non-complementary region and the second non-complementary region are not complementary, and wherein the first yoke region or the second yoke region comprise at least one nucleobase analogue.2. The polynucleotide of claim 1 , wherein the nucleobase analogue increases the Tm of binding the first yoke region to the second yoke region.3. The polynucleotide of claim 1 , wherein the nucleobase analogue is a locked nucleic acid (LNA) or a bridged nucleic acid (BNA).4. The polynucleotide of claim 1 , wherein the complementary first yoke region and second yoke region are each less than 15 bases in length.5. (canceled)6. (canceled)7. The polynucleotide of claim 1 , wherein the polynucleotide does not comprise a barcode or index sequence.8. A polynucleotide claim 1 , wherein the polynucleotide comprises:a duplex sample nucleic acid;a first polynucleotide ligated to a 5′ terminus of the duplex sample nucleic acid; anda second polynucleotide ligated to a 3′ terminus of the duplex sample nucleic acid, a first strand comprising a first terminal adapter region, a first non-complementary region, and a first yoke region; and', 'a second strand comprising a second terminal adapter region, a second ...

COMPOSITIONS AND METHODS TO PROMOTE ERYTHROPOIESIS

Described herein are compositions and methods for enhancing erythropoiesis in an individual in need thereof. Specifically agents that decrease the expression of Exosc10, such as inhibitory nucleic acid molecules, produce an increase in red blood cell production in the individual. 1. A method of enhancing erythropoiesis in an individual in need thereof , comprising administering an effective amount of an agent that decreases the expression of Exosc10 , wherein the agent produces an increase in red blood cell production in the individual , and wherein the agent is an inhibitory nucleic acid molecule that selectively decreases the expression of Exosc10.2. The method of claim 1 , wherein the individual is a human in need of treatment for an anemic disorder claim 1 , hemophilia claim 1 , thalassemia claim 1 , sickle cell disease claim 1 , bone marrow transplantation claim 1 , hematopoietic stem cell transplantation claim 1 , thrombocytopenia claim 1 , pancytopenia claim 1 , or hypoxia.3. The method of claim 2 , wherein the anemic disorder is associated with aging claim 2 , infectious disease claim 2 , chronic renal failure claim 2 , end-stage renal disease claim 2 , renal transplantation claim 2 , cancer claim 2 , AIDS claim 2 , antiviral therapy claim 2 , chronic stress claim 2 , chemotherapy claim 2 , radiation therapy claim 2 , bone marrow transplantation claim 2 , nutritional iron deficiency claim 2 , blood-loss claim 2 , hemolysis claim 2 , or is of genetic origin.4. The method of claim 3 , wherein the individual has a reduced hematocrit.5. The method of claim 1 , wherein the inhibitory nucleic acid molecule is a small interfering RNA claim 1 , an antisense RNA claim 1 , a ribozyme claim 1 , or a triple helix nucleic acid.6. The method of claim 5 , wherein the small interfering RNA is an siRNA or an shRNA.7. The method of claim 6 , wherein the small interfering RNA comprises 19 to 29 nucleotides that are substantially complementary to a sequence of 19 to 29 ...

COMPOSITIONS AND METHODS FOR ENHANCING HOMOLOGOUS RECOMBINATION

The present disclosure generally relates to compositions and methods for improving the efficiency of homologous recombination. In particular, the disclosure relates to reagents and the use of such reagents. 1. A method for performing homologous recombination , the method comprising:(a) generating a double-stranded break in a nucleic acid molecule present inside a cell to produce a cleaved nucleic acid molecule, and(b) contacting the cleaved nucleic acid molecule generated in (a) with a donor nucleic acid molecule,wherein the cleaved nucleic acid molecule and the donor nucleic acid molecule each contain matched termini on at least one end,wherein the matched termini on at least one end of the cleaved nucleic acid molecule and the donor nucleic acid molecule is at least ten nucleotides in length, andwherein the matched region of the cleaved nucleic acid molecule is single-stranded or double-stranded and the matched region of the donor nucleic acid molecule is single-stranded.2. The method of claim 1 , wherein the matched termini on at least one end of the cleaved nucleic acid molecule and the donor nucleic acid molecule have 5′ overhangs or 3′ overhangs.34.-. (canceled)54. The method of claim claim 1 , wherein the at least ten complementary nucleotides share at least 80% sequence identity.67.-. (canceled)8. The method of claim 1 , wherein the cleaved nucleic acid molecule has at least one terminus with a single-stranded region.12. The method of claim 1 , wherein donor nucleic acid molecule contains one or more nuclease resistant groups in at least one strand of at least one terminus.13. The method of claim 12 , wherein donor nucleic acid molecule contains one or more nuclease resistant groups in both strands of both termini.14. The method of claim 12 , wherein donor nucleic acid molecule contains a single terminal phosphorothioate linkage in both strands of both termini.15. The method of claim 12 , wherein donor nucleic acid molecule contains two terminal ...

HYBRID OLIGONUCLEOTIDES AND USES THEREOF

Provided herein are hybrid oligonucleotides comprising a region that promotes cleavage of a nucleic acid and a region that protects a nucleic acid from exonuclease activity. Such hybrid oligonucleotides are useful for modulating the expression of genes. Related compositions and methods are also provided. In some embodiments, methods are provided for treating a disease, such as by administering a hybrid oligonucleotide. 1. A composition comprising: [{'br': None, 'sub': m', 'n', 'o, 'sup': 1', '2', '3, '(X-X-X),'}, {'sup': 1', '3', '1', '3', '2', '2, 'wherein each instance of X, Xis independently a modified or unmodified nucleotide, wherein m and o are independently integers in a range of 1 to 10, reflecting the number of instances of Xand X, respectively, linked consecutively together through internucleotide linkages, wherein each instance of Xis a deoxyribonucleotide, wherein n is an integer in a range of 6 to 20, reflecting the number of instances of Xlinked consecutively together through internucleotide linkages; and'}], '(i) a first single stranded oligonucleotide having the general formula [{'br': None, 'sup': 4', '5, 'sub': q', 'r, '(X-X),'}, {'sup': 4', '5', '4', '5', '4', '5', '4', '5', '4', '5, 'sub': p', 'q', 'p', 'q, 'wherein each instance of Xis a modified or unmodified nucleotide, wherein each instance of Xis a deoxyribonucleotide, wherein p and q are independently 0 or 1, reflecting the number of instances of Xand X, respectively, wherein at least one of Xand Xis present in each instance of the unit, (X-X), wherein r is an integer from 2 to 20 reflecting the number of instances of the unit, (X-X), linked together through internucleotide linkages, wherein the second single stranded oligonucleotide does not contain a sequence of more than 5 consecutive deoxyribonucleotides, and wherein the symbol “-” denotes an internucleotide linkage.'}], '(ii) a second single stranded oligonucleotide of 4 to 40 nucleotides in length having the general formula2. The ...

Compositions and methods to promote erythropoiesis

Described herein are compositions and methods for enhancing erythropoiesis in an individual in need thereof. Specifically agents that decrease the expression of Exosc8, Exosc9, Dis3, Dis3L or Exosc10, such as inhibitory nucleic acid molecules, produce an increase in red blood cell production in the individual.

Compositions and Methods for Treating Cancer, Inhibiting Cell Proliferation, and Inducing Cell Death

Quadruplex-forming guanine-rich nucleic acid sequences are useful in compositions and methods for inhibiting cellular growth and proliferation and inducing cell death. Compositions for treating a patient are provided, including (i) a safe and effective amount of a sequence having at least 80% nucleic acid identity with a sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO:3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12 and combinations thereof, and (ii) a carrier, wherein the isolated oligonucleotide forms at least one quadruplex. 1. A composition for treating a patient , comprising: (i) a safe and effective amount of at least one isolated oligonucleotide comprising a sequence having at least 80% nucleic acid sequence identity with a sequence selected from the group consisting of SEQ ID NO: 1 , SEQ ID NO: 2 , SEQ ID NO:3 , SEQ ID NO: 4 , SEQ ID NO: 5 , SEQ ID NO: 6 , SEQ ID NO: 7 , SEQ ID NO: 8 , SEQ ID NO: 9 , SEQ ID NO:10 , SEQ ID NO:11 , SEQ ID NO:12 and combinations thereof , and (ii) a carrier , wherein the isolated oligonucleotide forms at least one quadruplex.2. The composition of claim 1 , comprising at least two isolated oligonucleotides claim 1 , each oligonucleotide comprising a sequence having at least 80% nucleic acid sequence identity with a sequence selected from the group consisting of SEQ ID NO: 1 claim 1 , SEQ ID NO: 2 claim 1 , SEQ ID NO:3 claim 1 , SEQ ID NO: 4 claim 1 , SEQ ID NO: 5 claim 1 , SEQ ID NO: 6 claim 1 , SEQ ID NO: 7 claim 1 , SEQ ID NO: 8 claim 1 , SEQ ID NO: 9 claim 1 , SEQ ID NO:10 claim 1 , SEQ ID NO:11 claim 1 , and SEQ ID NO:12 wherein each of said isolated oligonucleotides forms at least one quadruplex.3. The composition of claim 1 , comprising at least three isolated oligonucleotides claim 1 , each oligonucleotide comprising a sequence having at least 80% nucleic acid sequence identity with a sequence selected from ...

CHIMERIC DOUBLE-STRANDED NUCLEIC ACID

A method of reducing the level of a transcription product in a cell comprising contacting with the cell a composition comprising a double-stranded nucleic acid complex comprising a first nucleic acid strand annealed to a second nucleic acid strand, wherein: (i) the first nucleic acid strand hybridizes to the transcription product and comprises (a) a region consisting of at least 4 consecutive nucleotides that are recognized by RNase H when the strand is hybridized to the transcription product, (b) one or more nucleotide analogs located on 5′ terminal side of the region, (c) one or more nucleotide analogs located on 3′ terminal side of the region and (d) a total number of nucleotides and nucleotide analogs ranging from 8 to 35 nucleotides and (ii) the second nucleic acid strand comprises (a) nucleotides and optionally nucleotide analogs and (b) at least 4 consecutive RNA nucleotides. 1. A composition comprising a double-stranded nucleic acid complex comprising a first nucleic acid strand annealed to a second nucleic acid strand , wherein: (a) a region consisting of at least 4 consecutive nucleotides that are recognized by RNase H when the strand is hybridized to the target transcription product,', '(b) one or more nucleotides and one or more nucleotide analogs, wherein the total number of the nucleotides and the nucleotide analogs range from 8 to 100 nucleotides and, '(i) the first nucleic acid strand is capable of hybridizing to a target transcription product, wherein the first nucleic acid strand comprises '(a) nucleotides and optionally nucleotide analogs.', '(ii) the second nucleic acid strand comprises2. The composition according to claim 1 , wherein the second nucleic acid strand comprises:(a) an RNA nucleotide and optionally a nucleotide analog, and optionally a DNA nucleotide; or(b) a DNA nucleotide and/or a nucleotide analog; or(c) PNA nucleotides.3. The composition according to claim 1 , wherein the second nucleic acid strand is cleavable by RNaseH in a ...

COMPLEMENT COMPONENT C5 iRNA COMPOSITIONS AND METHODS OF USE THEREOF

The invention relates to iRNA, e.g., double stranded ribonucleic acid (dsRNA), compositions targeting the complement component C5 gene, and methods of using such iRNA, e.g., dsRNA, compositions to inhibit expression of C5 and to treat subjects having a complement component C5-associated disease, e.g., paroxysmal nocturnal hemoglobinuria. 1. A method of treating a human subject having a disease or disorder that would benefit from reduction in complement component C5 expression , the method comprising administering to the subject a therapeutically effective fixed dose of a double stranded ribonucleic acid (dsRNA) agent for inhibiting expression of complement component C5 selected from the group consisting of(a) a dsRNA agent comprising a sense strand and an antisense strand, wherein the sense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO:1 and the antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO:5;(b) a dsRNA agent comprising a sense strand and an antisense strand, the antisense strand comprising a region of complementarity which comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from any one of the antisense sequences listed in any one of Tables 3, 4, 5, 6, 18, 19, 20, 21, and 23;(c) a dsRNA agent comprising a sense strand and an antisense strand forming a double stranded region,wherein the sense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO:1 and the antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO:5,wherein substantially all of the nucleotides of the sense strand and substantially all of the nucleotides of the antisense strand are modified nucleotides, andwherein the sense ...

Antisens oligonucleotides for the treatment of leber congenital amaurosis

The present invention relates to the fields of medicine and immunology. In particular, it relates to novel antisense oligonucleotides that may be used in the treatment, prevention and/or delay of Leber congenital amaurosis.

Compositions and methods for enhancing homologous recombination

The present disclosure generally relates to compositions and methods for improving the efficiency of homologous recombination. In particular, the disclosure relates to reagents and the use of such reagents.

NUCLEIC ACID MAZZOCCHIO AND METHODS OF MAKING AND USE THEREOF

Provided herein are compositions and methods involving nucleic acid nanostructures that can encapsulate cargo for use in, for example, therapeutic, diagnostic, and analytical applications. The nanostructures can have a plurality of interconnected subunits configured such that the nanostructures have a continuous torus-like structure with a closed three-dimensional cavity. Preferably, the nanostructure is a nucleic acid mazzocchio. The subunits are connected by linkers having defined lengths to constrain the nanostructure into the continuous torus-like shape. The closed three-dimensional cavity is of defined size to encapsulate any cargo of interest. Cargo can also be positioned in the open hole at the center of the nanostructure. The cargo can be a wide range of compounds including, for example, chemical drugs, small molecules, therapeutics, targeting agents, enzymes, dyes, and fluorescent molecules. As such, the disclosed nanostructures are suitable for delivery of one or more therapeutic, toxic, imaging, diagnostic, or prophylactic agents. 1. A nucleic acid nanostructure having a continuous torus-like structure with a closed three-dimensional cavity , the nanostructure comprising a plurality of subunits ,wherein each of the subunits comprises a core domain and a connecting domain, wherein the core domain defines a polygon having a plurality of edges that enclose an open area, wherein the edges and open area define a plane of the subunit, wherein the connecting domain comprises one or more linkers,wherein a first edge of each subunit is coplanar with the first edges of the other subunits, wherein each of the subunits is between and connected to two other of the subunits with the planes of the connected subunits facing each other thereby forming a stack of subunits, wherein the planes of the connected subunits are substantially perpendicular to the plane of the first edges of the subunits and are tilted relative to the subunits connected to a given subunit in the ...

Aptamers against clostridium difficile, compositions comprising aptamers against clostridium difficile and methods of using the same

Compositions comprising optimized aptamers capable of specifically binding to a surface protein of Clostridium difficile spore are provided. A method for detecting, enriching, separating, and/or isolating Clostridium difficile spores is provided.

COMPOSITIONS AND METHODS FOR TREATING SICKLE CELL DISEASE

Peptide nucleic acid (PNA) oligomers that target the β-globin gene and can increase the frequency of recombination of donor oligonucleotide at the site of a Sickle Cell Disease mutation are provided. Nanoparticle formulations for delivering the PNA oligomers and donor oligonucleotides, and potentiating agents for increase the frequency of recombination of the donor oligonucleotide are also provided. Methods of using the PNA oligomers, donor oligonucleotides, nanoparticles, and potentiating agents for treating Sickle Cell Disease are also provided. 1. A nanoparticle comprisinga core comprising a polyhydroxyester polymer selected from poly(lactic acid), poly(glycolic acid), and poly(lactic acid-co-glycolic acid);a shell comprising a hyperbranched polyglycerol (HPG); anda plurality of a peptide nucleic acid (PNA) oligomer entrapped or encapsulated therein, the PNA oligomer comprisinga Hoogsteen binding peptide nucleic acid segment comprising PNA residues comprising the nucleic acid sequence TTJJTJT and a Watson-Crick binding PNA segment comprising PNA residues comprising the nucleic acid sequence TCTCCTTAAACCTGT (SEQ ID NO:1), TCTCCTTAAACCTGTCTT (SEQ ID NO:2), ora variant thereof comprising a combination of up to 5 nucleic acid sequence substitutions, additions, insertions, or deletions in the Hoogsteen binding PNA segment, the Watson-Crick binding segment, or the combination thereof,wherein the two segments can bind or hybridize to a target region in the β-globin gene and induce strand invasion, displacement, and formation of a triple-stranded molecule among the two PNA segments and the target region.2. The nanoparticle of claim 1 , wherein the PNA oligomer comprises the nucleic acid sequence TTJJTJT-linker-TCTCCTTAAACCTGT (SEQ ID NO:3) or TTJJTJT-linker-TCTCCTTAAACCTGTCTT (SEQ ID NO:4) claim 1 , wherein “linker” is a flexible linker claim 1 , linking the Hoogsteen binding segment to the Watson-Crick binding segment.or a variant thereof comprising a combination of up ...

PRODUCTION OF STABLE NON-POLYADENYLATED RNAS

The invention relates in aspects to hybrid RNAs lacking a poly-A tail and nucleic acid vectors for expressing the RNA. The hybrid RNAs in some instances have a stabilizing triple helical structure. Related methods for expressing RNA in vivo and in vitro are also disclosed. 171.-. (canceled)72. A method for expressing an RNA lacking a poly-A tail , comprising:expressing in a cell an isolated nucleic acid comprising an RNA having a 3′ heterologous terminal sequence and lacking a poly A tail.73. The method of claim 72 , wherein the isolated nucleic acid is expressed in vivo.74. The method of claim 72 , wherein the isolated nucleic acid is expressed ex vivo.75. The method of claim 72 , wherein the RNA encodes a protein.76. The method of claim 75 , wherein the protein is an immunogenic protein.77. The method of claim 75 , wherein the immunogenic protein is a viral protein or a cancer protein.78. A hybrid nucleic acid comprising:an RNA molecule, lacking a poly-A tail, linked to a heterologous RNA stabilizing terminal sequence, wherein the RNA molecule encodes an immunogenic protein.79. The hybrid nucleic acid of claim 78 , wherein the heterologous RNA stabilizing terminal sequence has a triple helix conformation.80. The hybrid nucleic acid of claim 78 , wherein the RNA molecule is a mRNA which lacks a poly-A tail.81. The hybrid nucleic acid of claim 78 , wherein the RNA molecule is a noncoding RNA.82. The hybrid nucleic acid of claim 78 , wherein nucleic acid includes at least one chemical or natural modification.83. A composition comprising:an RNA molecule, lacking a poly-A tail, linked to a heterologous RNA stabilizing terminal sequence, formulated in a nanoparticle.84. The composition of claim 83 , wherein nucleic acid includes at least one chemical or natural modification.85. The composition of claim 83 , wherein the heterologous RNA stabilizing terminal sequence has a triple helix conformation.86. The composition of claim 83 , wherein the RNA molecule is a mRNA which ...

COMPOSITIONS AND METHODS FOR DELIVERY OF NUCLEIC ACIDS

The present disclosure relates to methods and compositions for modulating protein expression. In particular, the invention features methods and compositions for increasing protein expression in a cell by delivering to the cell a composition including an mRNA encoding a polypeptide and one or more oligonucleotides, wherein each of the one or more oligonucleotides includes a region of linked nucleotides complimentary to a portion of the sequence of the mRNA. The methods and compositions described herein may be used to modulate gene expression (e.g., increase gene expression), to increase the stability of the mRNA, to decrease the immunogenicity of the mRNA, to enable selective expression (e.g., in a target cell or tissue) of the mRNA, and/or to enable the delivery of two or more mRNAs in a stoichiometric ratio. 1. A composition comprising: (i) a 5′-cap structure;', '(ii) a 5′-untranslated region (5′-UTR);', '(iii) an open reading frame encoding the polypeptide;', '(iv) a 3′-untranslated region (3′-UTR); and', '(v) a poly-A region; and, '(a) an mRNA encoding a polypeptide comprising(b) three or more oligonucleotides, wherein each oligonucleotide comprises a region of linked nucleotides complimentary to a different portion of the sequence of the mRNA.2. The composition of claim 1 , wherein:a) the three or more oligonucleotides comprise at least three and no more than ten oligonucleotides;b) the three or more oligonucleotides comprise at least ten and no more than fifty oligonucleotides;c) the three or more oligonucleotides collectively comprise regions of linked nucleotides complementary to 10% or more of the sequence of the mRNA;d) the three or more oligonucleotides each comprise between 6 and 100 nucleotides;e) the three or more oligonucleotides comprise a region of linked nucleotides complementary to a portion of a sequence of the mRNA, wherein the region of linked nucleotides is at least 5 nucleotides;{'sub': '2', 'f) the three or more oligonucleotides comprise at ...

COMPLEMENT COMPONENT C5 iRNA COMPOSITIONS AND METHODS OF USE THEREOF

The invention relates to iRNA, e.g., double stranded ribonucleic acid (dsRNA), compositions targeting the complement component C5 gene, and methods of using such iRNA, e.g., dsRNA, compositions to inhibit expression of C5 and to treat subjects having a complement component C5-associated disease, e.g., paroxysmal nocturnal hemoglobinuria.

SELF ASSEMBLING NUCLEIC ACID NANOSTRUCTURES

Stable self-assembling nucleic acid nanostructures comprising: —a plurality of oligonucleotides, —a plurality of G-quadruplex forming nucleic acids linked to the plurality of oligonucleotides, and —a plurality of G-quadruplex stabilizing domains linked to the G-quadruplex forming nucleic acids. The nucleic acid nanostructures are suitable for use as agonists or antagonists of nucleic acid interacting complexes, such as Toll-like receptors; for inhibiting DNA or RNA expression; for stimulating or inhibiting an immune response; and for treating diseases such as cancer, infectious diseases, allergies and allergic diseases, and autoimmune diseases. 1. A stable self-assembling nucleic acid nanostructure , comprisinga plurality of oligonucleotides, wherein each internucleotide linkage of the oligonucleotide is not a phosphorothioate linkage,a plurality of G-quadruplex forming nucleic acids linked to the plurality of oligonucleotides, wherein the G-quadruplex forming nucleic acids is not TAGGGTT, anda plurality of G-quadruplex stabilizing domains linked to the G-quadruplex forming nucleic acids,wherein the oligonucleotides, the G-quadruplex forming nucleic acids and the G-quadruplex stabilizing domains form a plurality of G-quad structures.2. A stable self-assembling nucleic acid nanostructure , comprisinga plurality of oligonucleotides,a plurality of G-quadruplex forming nucleic acids linked to the plurality of oligonucleotides, wherein the G-quadruplex forming nucleic acids is not TAGGGTT, anda plurality of G-quadruplex stabilizing domains linked to the G-quadruplex forming nucleic acids,wherein when at least one of the G-quadruplex forming nucleic acids comprises GG, GGG, or GGGG and the oligonucleotide is CpG oligonucleotide the lipid is not diacyl lipid, wherein the oligonucleotides, the G-quadruplex forming nucleic acids and the G-quadruplex stabilizing domains form a plurality of G-quad structures.3. The nanostructure of claim 1 , wherein the self-assembling nucleic ...

Compositions and methods for next generation sequencing

Provided herein are compositions and methods for next generation sequencing using universal polynucleotide adapters. Further provided are universal adapters using locked nucleic acids or bridged nucleic acids. Further provided are barcoded primers of reduced length for extension of universal adapters. Further provided herein are universal adapter blockers.

G-RICH isoDNA SEQUENCES FORMING G-QUADRUPLEX STRUCTURE, THEIR FUNCTION AS APTAMERS AND A PROCESS FOR THE PREPARATION THEREOF

The present invention relates to G-quadruplex forming isoDNA aptamers and a process for the preparation thereof. The present invention further relates to a stable, non-genetic, guanine rich 2′-5′ linked isoDNA selected from 3′ deoxy 2′-5′ isoDNA and 3′ deoxy 2′-5′ isoDNA-isoRNA hybrid. The instant 2′-5′ linked isoDNA such as the thrombin binding aptamer (isoTBA) can be used in deep vein thrombosis, where prolonged anticoagulant activity is required. 1) G-qudruplex forming isoDNA oligomers comprising a stable , non-genetic , guanine rich 2′-5′ linked iso DNA sequences selected from 3′ deoxy 2′-5′ isoDNA and 3′ deoxy 2′-5′ isoDNA-isoRNA hybrid.2) The sequence according to claim 1 , wherein the said 2′-5′ linked iso DNA forms unimolecular antiparallel G quadruplexes.3) The sequence according to claim 1 , wherein the said 2′-5′ linked iso DNA optionally forms hybrids with isoRNA.5) The isoDNA sequences according to claim 4 , wherein the 2′-5′ linked isoDNA sequence No. 2 or 3 is binding to thrombin.6) The sequence as claimed in wherein said isoDNA sequence is for use in the preparation of a medicament for the treatment of deep vein thrombosis.7) A process for synthesis of G-quadruplex forming isoDNA sequence as claimed in claim 1 , wherein said process comprises the steps of:a) synthesizing 3′-5′-oligonucleotides having Seq ID No. 1 by β-cyanoethyl phosphoramidite chemistry;b) replacing the 3′-5′-phosphodiester linkages in Seq ID no. 1 (dTBA-1) by 2′-5′-phosphodiester linkages to obtain 3′-deoxy-2′-5′ oligomer 5′-GGTTGGTGTGGTTGG-2′ Seq ID No 2 (isod-TBA-2);c) replacing 3′-deoxythymidine in the TGT loop (T7 and T9 in isod-TBA-2) by uridine to obtain UGU loop-modified sequence isod-TBA-3 (Seq ID No: 3); removing 3′deoxyguanosine (G) at position G8 (TGT loop) in sequence ID No 2, to obtain TT loop in 14 mer sequence having Seq ID No. 4; removing T4 and T13 in sequence ID No. 2 to obtain 13 mer sequence having Seq ID No. 5; removing T4, G8, T9 and T13 in sequence ID No 2 to ...

TETRAMOLECULAR PARALLEL G-QUADRUPLEX-FORMING HYDROPHOBICALLY MODIFIED OLIGONUCLEOTIDES

The present invention relates to tetramolecular parallel G-quadruplex-forming oligonucleotides. If G-quadruplexes are of prime importance in biology, their use is hampered by the propensity of G4-prone DNA molecules, in particular G4-prone DNA molecules of long size, to adopt many different G4 topological conformations or other alternative foldings. By introducing a lipid modification at the end of the oligonucleotide, the inventors succeeded in obtaining long tetramolecular parallel G-quadruplexes (tpG4). The present invention thus concerns an oligonucleotide modified by substitution at the 5′ or the 3′ end by a lipid moiety, wherein said oligonucleotide comprises a nucleic acid sequence of at least 10 nucleotides, said nucleic acid sequence including a series of at least 4 consecutive guanine residues located in the middle of said sequence. A tetramolecular parallel G-quadruplex comprising 4 identical modified oligonucleotides as defined above, wherein each of the 4 consecutive guanine residues included in the middle of the nucleic acid sequence of each oligonucleotide respectively form G-quartets with the corresponding guanine residues of the other 3 oligonucleotides, said G-quartets being stabilized by π-π staking and Hoogsteen hydrogen bonding, is also contemplated. The modified oligonucleotides have preferably the general formula (I) or (II), wherein the oligonucleotides are modified by substitution at the 5′ or the 3′ end by a lipid moiety, and said oligonucleotides comprise a nucleic acid sequence of at least 10 nucleotides, said nucleic acid sequence including a series of at least 4 consecutive guanine residues located in the middle of said sequence. 1. An oligonucleotide modified by substitution at the 5′ or the 3′ end by a lipid moiety , wherein said oligonucleotide comprises a nucleic acid sequence of at least 10 nucleotides , said nucleic acid sequence including a series of at least 4 consecutive guanine residues located in the middle of said sequence.2 ...

METHODS FOR INDUCING GLUCOSE UPTAKE

The present invention provides a method for inducing glucose uptake in a muscle cell by inhibiting Trim32 protein in the cell and to a method for inducing glucose uptake in a muscle cell, by increasing the abundance of plakoglobin protein in the cell. 1. A method for inducing glucose uptake in a muscle cell , comprising the step of inhibiting Trim32 protein in said cell , thereby inducing glucose uptake in a muscle cell.2. The method of claim 1 , wherein said muscle cell is a skeletal muscle cell.3. The method of claim 1 , wherein said inhibiting Trim32 in said cell is further inducing muscle fiber growth.4. The method of claim 1 , wherein said inhibiting Trim32 in said cell is inducing the phosphorylation of insulin receptor in said cell.5. The method of claim 1 , wherein said inhibiting Trim32 is inducing the accumulation of plakoglobin.6. The method of claim 1 , wherein said inhibiting Trim32 in said cell is expressing a dominant negative Trim 32 protein in said cell.7. The method of claim 1 , wherein said inhibiting Trim32 in said cell is delivering an anti-Trim 32 antibody into said cell.8. The method of claim 6 , wherein said expressing a dominant negative Trim 32 protein in said cell is inserting a synthetic mRNA molecule encoding said dominant negative Trim 32 protein into said cell claim 6 , said synthetic mRNA molecule comprises 5-methylcytidine bases claim 6 , pseudouridine bases claim 6 , or a combination thereof.9. The method of claim 6 , wherein said expressing a dominant negative Trim 32 protein in said cell is delivering a nucleic acid molecule encoding said dominant negative Trim 32 protein via electroporation into said cell.10. The method of claim 6 , wherein said expressing a dominant negative Trim 32 protein in said cell is delivering a nucleic acid molecule encoding said dominant negative Trim 32 protein via a cationic vector into said cell.11. A method for inducing glucose uptake in a muscle cell claim 6 , comprising the step of increasing the ...

METHOD FOR TREATING CARDIOVASCULAR DISEASE

The invention relates to a method of treating a cardiovascular disease, such as heart failure, in a subject in need comprising the step of administering an inhibitor of bZIP repressor or an activator of p38 or a combination thereof to a subject in need thereby treating the cardiovascular disease. The inhibitor to bZIP repressor is: an inhibitor of ATF3; an inhibitor of JDP2; a co-inhibitor to both ATF3 and JDP2; or a combination of an inhibitor of ATF3 and an inhibitor of JDP2. 1. A method of treating a cardiovascular disease in a subject in need comprising the step of administering an inhibitor of bZIP repressor or an activator of p38 or a combination thereof to a subject in need thereby treating the cardiovascular disease.2. The method of claim 1 , wherein the inhibitor to bZIP repressor is:an inhibitor of ATF3;an inhibitor of JDP2;a co-inhibitor to both ATF3 and JDP2; ora combination of an inhibitor of ATF3 and an inhibitor of JDP2.3. The method of claim 2 , wherein the inhibitor to ATF3 and the inhibitor to JDP2 are administered simultaneously or sequentially.4. The method of claim 1 , wherein the inhibitor is a protein claim 1 , a peptide claim 1 , a small molecule or an agent claim 1 , which prevents or reduces the expression of the bZIP repressor.5. The method of claim 1 , wherein the activator of p38 is a protein claim 1 , a peptide claim 1 , a small molecule or an agent claim 1 , which increases the activity of the p38.6. The method of claim 4 , wherein the agent which decreases the expression of the bZIP repressor is an inhibitor of the mRNA encoding the bZIP repressor.7. The method of claim 6 , wherein the inhibitor of the mRNA encoding the bZIP repressor is an antisense RNA claim 6 , triple helix molecule claim 6 , ribozyme claim 6 , microRNA claim 6 , or siRNA that recognizes the bZIP repressor mRNA.8. The method of claim 5 , wherein the agent which increases the expression of the p38 is an mRNA encoding the p38 or an activator thereof.9. The method of ...

THERAPEUTIC RNA SWITCHES COMPOSITIONS AND METHODS OF USE

The invention provides for therapeutic RNA switches comprising oligonucleotide sequences complementary to a trigger sequence, an antisense strand oligonucleotide, and a sense strand oligonucleotide complementary to a target nucleic acid molecule. 1. A therapeutic RNA switch comprising:at least one polynucleotide sequence that can bind to a trigger sequence; andan antisense oligonucleotide and a sense oligonucleotide in which the antisense oligonucleotide is complementary to a target RNA, wherein the RNA switch can switch between an inactive state and an active state in the presence of the trigger sequence.2. The therapeutic RNA switch of claim 1 , wherein in the inactive state no partially formed siRNA-like helices exist.3. The therapeutic RNA switch of claims 1 , wherein the therapeutic RNA switch undergoes a conformational change in the presence of the trigger sequence which causes the antisense and sense oligonucleotides to form an siRNA-like helix.4. The therapeutic RNA switch of claim 3 , wherein the siRNA-like molecule reduces or inhibits the target RNA.5. A two-strand therapeutic RNA switch comprising:a complex between an adapter polynucleotide strand and a protofunctional polynucleotide strand, wherein the adapter polynucleotide can bind a trigger sequence and the protofunctional polynucleotide strand forms an siRNA-like RNA double helix when the adapter polynucleotide strand binds the trigger sequence.6. The two-strand therapeutic RNA switch of claim 5 , wherein the siRNA-like RNA double helix comprises an antisense oligonucleotide and a sense oligonucleotide in which the antisense oligonucleotide is complementary to a target RNA.7. The two-strand therapeutic RNA switch of claim 5 , wherein in the absence of a trigger sequence no partially formed siRNA-like helices exist.8. The two-strand therapeutic RNA switch of claim 5 , wherein the siRNA-like RNA double helix reduces or inhibits the target RNA.9. A four-strand therapeutic RNA/DNA hybrid complex ...

Circularized engineered rna and methods

A circular RNA molecule generally includes at least one coding region and an internal ribosome entry site (IRES) operably linked to the coding region. The RNA may be more resistant to digestion by an RNA endonuclease that a linear form of the circular RNA. In another aspect, a polynucleotide generally includes a transcription unit and a promoter operably linked to the transcription unit. The transcription unit includes a circularizing element, at least one coding region and an internal ribosome entry site (IRES) operably linked to the coding region. When transcribed by a cell, the transcribed RNA forms a circular RNA molecule.

NICKED OR GAPPED NUCLEIC ACID MOLECULES AND USES THEREOF

The present disclosure provides meroduplex (nicked or gapped) ribonucleic acid molecules (mdRNA) that decreases or silences target gene expression. An mdRNA of this disclosure comprises at least three strands that combine to form at least two non-overlapping double-stranded regions separated by a nick or gap wherein one strand is complementary to a target gene RNA. In addition, the meroduplex may have one or more modifications or substitutions, such as nucleotide base, sugar, terminal cap structure, internucleotide linkage, or any combination of such modifications. Also provided are methods of decreasing expression of a target gene in a cell or in a subject to treat a disease related to altered expression of a target gene. 164.-. (canceled)65. A method for reducing expression of a target gene in a cell , said method comprising:contacting a target gene expressing cell with a composition comprising a 19 to 30 base pair double-stranded ribonucleic acid, wherein said target gene expression is reduced as a consequence of contacting said cell with said composition, said ribonucleic acid comprising(a) an A strand having a length of 15 to 30 nucleotides and a nucleotide sequence that is complementary to a nucleotide sequence in said target gene;(b) an S1 strand having a length of 5 to 25 nucleotides, wherein said S1 strand anneals to said A strand thereby forming a first double-stranded region of 5 to 15 base pairs; and(c) an S2 strand having a length of 5 to 25 nucleotides, wherein said S2 strand anneals to said A strand thereby forming a second double-stranded region of 3 to 25 base pairs and wherein said annealed S2 strand is separated from said annealed S1 strand by a nick or a gap.66. The method of wherein said composition comprises a liposome claim 65 , a hydrogel claim 65 , a cyclodextrin claim 65 , a biodegradable nanocapsule claim 65 , a bioadhesive microsphere claim 65 , or a proteinaceous vector.67. The method of wherein said liposome is a surface-modified ...

Antisense oligonucleotides for the treatment of leber congenital amaurosis

The present invention relates to the fields of medicine and immunology. In particular, it relates to novel antisense oligonucleotides that may be used in the treatment, prevention and/or delay of Leber congenital amaurosis.

MODIFIED DNA QUADRUPLEX-FORMING OLIGONUCLEOTIDES AND METHODS OF USE

Oligonucleotides according to the following Formula I are provided herein: 5′-X-Q-Y-3′ wherein X and Y are each independently selected from the group consisting of a lipid and a polyethylene glycol; Q is a quadruplex-forming guanine-rich promoter gene oligonucleotide (GPGO); a is 0 or 1; and b is 0 or 1, wherein the sum of a+b=1 or 2. Also provided are compositions including Formula I oligonucleotides and methods of their use in inhibiting cell growth, treating cancer, and treating tumors. 1. An oligonucleotide according to the following Formula I:{'br': None, 'sub': a', 'b, '5′-X-Q-Y-3′\u2003\u2003 Formula I'}wherein:X and Y are each independently selected from the group consisting of a lipid and a polyethylene glycol;Q is a quadruplex-forming guanine-rich promoter gene oligonucleotide (GPGO);a is 0 or 1; andb is 0 or 1,wherein the sum of a+b=1 or 2.5. The oligonucleotide of claim 4 , wherein Q is a GPGO derived from an oncogene selected from the group consisting of c-Myc claim 4 , c-Myb claim 4 , VEGF claim 4 , Bcl-2 claim 4 , K-ras claim 4 , HIF-1α claim 4 , Rb claim 4 , RET claim 4 , c-Kit claim 4 , and PDGF-A.6. The oligonucleotide of claim 5 , wherein Q is a c-Myc sequence selected from the group consisting of SEQ ID NO: 1 claim 5 , SEQ ID NO: 2 claim 5 , SEQ ID NO: 3 claim 5 , SEQ ID NO: 4 claim 5 , SEQ ID NO: 5 claim 5 , SEQ ID NO: 6 claim 5 , SEQ ID NO: 7 claim 5 , SEQ ID NO: 8 claim 5 , SEQ ID NO: 9 claim 5 , SEQ ID NO: 10 claim 5 , SEQ ID NO: 11 claim 5 , SEQ ID NO: 12 claim 5 , SEQ ID NO: 13 claim 5 , and SEQ ID NO: 14; a is 1; and b is 0.7. The oligonucleotide of claim 5 , wherein Q is a c-Myb sequence selected from the group consisting of SEQ ID NO: 15 claim 5 , SEQ ID NO: 16 claim 5 , SEQ ID NO: 17 claim 5 , SEQ ID NO: 18 claim 5 , SEQ ID NO: 19 claim 5 , and SEQ ID NO: 20; a is 1; and b is 0.15. The oligonucleotide of claim 5 , wherein Q is a sequence selected from the group consisting of SEQ ID NOs: 1-70; a is 0; and b is 1.16. A composition ...

APTAMER CAPABLE OF BINDING TO HGF RECEPTOR

Provided is an aptamer including a polynucleotide of any of the following (a) to (c) and capable of binding to an HGF receptor to exhibit an activity of inhibiting the binding of HGF to the HGF receptor. (a) A polynucleotide consisting of a base sequence set forth in SEQ ID NO: 1, (b) A polynucleotide consisting of a base sequence having the deletion, substitution, insertion and/or addition of one to several bases in the base sequence set forth in SEQ ID NO: 1, and (c) A polynucleotide consisting of a base sequence having a sequence identity of 80% or more to the base sequence set forth in SEQ ID NO: 1. 1. An aptamer comprising a polynucleotide of any of the following (a) to (c) and capable of binding to an HGF receptor to exhibit an activity of inhibiting the binding of HGF to the HGF receptor ,(a) a polynucleotide consisting of a base sequence set forth in SEQ ID NO: 1,(b) a polynucleotide consisting of a base sequence having the deletion, substitution, insertion and/or addition of one to several bases in the base sequence set forth in SEQ ID NO: 1, and(c) a polynucleotide consisting of a base sequence having a sequence identity of 80% or more to the base sequence set forth in SEQ ID NO: 1.2. The aptamer according to claim 1 , which has a loop structure at least a part of which is formed of the polynucleotide of any of (a) to (c).3. The aptamer according to claim 2 , which has a stem structure consisting of a double-stranded polynucleotide connected to the loop structure.4. The aptamer according to claim 2 , wherein the loop structure consists of a polynucleotide chain having 28 to 40 bases.5. The aptamer according to claim 1 , wherein the polynucleotide of (a) to (c) forms a guanine quadruplex structure.6. An aptamer having a multi-structure in which two or more polynucleotides of any of the following (a) to (c) are connected and capable of binding to an HGF receptor to exhibit an activity of activating the HGF receptor claim 1 ,(a) a polynucleotide consisting of ...

CHIMERIC DOUBLE-STRANDED NUCLEIC ACID

A method of reducing the level of a transcription product in a cell comprising contacting with the cell a composition comprising a double-stranded nucleic acid complex comprising a first nucleic acid strand annealed to a second nucleic acid strand, wherein: (i) the first nucleic acid strand hybridizes to the transcription product and comprises (a) a region consisting of at least 4 consecutive nucleotides that are recognized by RNase H when the strand is hybridized to the transcription product, (b) one or more nucleotide analogs located on 5′ terminal side of the region, (c) one or more nucleotide analogs located on 3′ terminal side of the region and (d) a total number of nucleotides and nucleotide analogs ranging from 8 to 35 nucleotides and (ii) the second nucleic acid strand comprises (a) nucleotides and optionally nucleotide analogs and (b) at least 4 consecutive RNA nucleotides. 2. The pharmaceutical composition according to claim 1 , wherein the first nucleic acid strand is further comprises (b) a 5′ wing region which comprises one or more nucleotide analogs or modified nucleotide analogs located 5′ to the at least 4 consecutive DNA nucleotides or modified DNA nucleotides that are recognized by RNase H; and/or (c) a 3′ wing region which comprises one or more nucleotide analogs or modified nucleotide analogs located 3′ to the at least 4 consecutive DNA nucleotides or modified DNA nucleotides that are recognized by RNase H.3. The pharmaceutical composition according to claim 1 , wherein the double stranded nucleic acid complex further comprises a third nucleic acid strand annealed to the second nucleic acid strand.4. The pharmaceutical composition according to claim 3 , wherein the third nucleic acid strand (i) comprises nucleotides and optionally nucleotide analogs and total number of the nucleotides and nucleotide analogs which are optionally comprised is 8 to 100 claim 3 , (ii) comprises at least 4 consecutive nucleotides that are recognized by RNase H when ...

COMPOSITIONS FOR ENHANCING TARGETED GENE EDITING AND METHODS OF USE THEREOF

Compositions and methods for enhancing targeted gene editing and methods of use thereof are disclosed. In the most preferred embodiments, gene editing is carried out utilizing a gene editing composition such as triplex-forming oligonucleotides, CRISPR, zinc finger nucleases, TALENS, or others, in combination with a gene modification potentiating agent such as stem cell factor (SCF), a CHK1 or ATR inhibitor, or a combination thereof. A particular preferred gene editing composition is triplex-forming peptide nucleic acids (PNAs) substituted at the γ position for increased DNA binding affinity. Nanoparticle compositions for intracellular delivery of the gene editing composition are also provided and particular advantageous for use with in vivo applications. 1. A triplex forming composition comprising a Hoogsteen binding peptide nucleic acid (PNA) segment and a Watson-Crick binding PNA segment collectively totaling no more than 50 nucleobases in length , wherein the two segments can bind or hybridize to a target region comprising a polypurine stretch in a cell's genome to induce strand invasion , displacement , and formation of a triple-stranded molecule among the two PNA segments and the polypurine stretch of the cell's genome ,wherein the Hoogsteen binding segment binds to the target duplex by Hoogsteen binding for a length of least five nucleobases,wherein the Watson-Crick binding segment binds to the target duplex by Watson-Crick binding for a length of least five nucleobases, andwherein one or more of the PNA residues are γPNA residues,wherein the Hoogsteen binding segment optionally comprises one or more chemically modified cytosines selected from the group consisting of pseudocytosine, pseudoisocytosine, and 5-methylcytosine, andwherein the two segments are optionally linked by a linker.25.-. (canceled)6. The triplex forming composition of claim 1 , wherein the segments can form a triple-stranded molecule with a region of the beta-globin gene comprising the ...

METHODS AND COMPOSITIONS FOR MODULATING GENE EXPRESSION

The present technology relates to compositions and methods for modulating expression of genes which include a target oligonucleotide sequence, such as repeats of a particular oligonucleotide sequence containing 3 to 10 nucleotides. In particular aspects, the present technology relates to agents having a formula A-L-B, wherein -L- is a linker; A- is a Brd4 binding moiety; and —B is a nucleic acid binding moiety, such as a polyamide or complementary oligonucleotide, that specifically binds to the target oligonucleotide sequence. 1. An agent having a formula A-L-B wherein -L- is a linker; A- is a Brd4 binding moiety; and —B is a nucleic acid binding moiety that specifically binds to one or more repeats of a target oligonucleotide sequence selected from the group consisting of CGG , CTG , and CCTG.2. The agent of claim 1 , wherein the —B is a polyamide that specifically binds to the one or more repeats of the target oligonucleotide sequence.3. The agent of claim 1 , wherein the —B is a second oligonucleotide sequence that specifically binds to the target oligonucleotide sequence.4. The agent of claim 2 , wherein the agent is capable of increasing mRNA levels produced from a gene comprising at least about 30 repeats of the oligonucleotide sequence.5. A pharmaceutical composition comprising a therapeutically effective amount of the agent of and a pharmaceutically acceptable carrier.6. A method for modulating mRNA levels produced from a gene in a cell comprising contacting the cell with an effective amount of the agent of claim 1 , wherein the gene comprises the target oligonucleotide sequence.7. The method of claim 6 , wherein the gene comprises at least about 30 repeats of the target oligonucleotide sequence.8. The method of claim 6 , wherein the mRNA levels are increased by at least about 2.5-fold relative to an untreated cell.9. A method for increasing levels of a protein in a cell claim 1 , comprising contacting the cell with an effective amount of the agent of claim ...

Production of stable non-polyadenylated rnas

The invention relates in aspects to hybrid RNAs lacking a poly-A tail and nucleic acid vectors for expressing the RNA. The hybrid RNAs in some instances have a 3′ terminal stabilizing triple helical structure. Related methods for expressing said RNAs in vivo and in vitro are also disclosed.

NICKED OR GAPPED NUCLEIC ACID MOLECULES AND USES THEREOF

The present disclosure provides meroduplex (nicked or gapped) ribonucleic acid molecules (mdRNA) that decreases or silences target gene expression. An mdRNA of this disclosure comprises at least three strands that combine to form at least two non-overlapping double-stranded regions separated by a nick or gap wherein one strand is complementary to a target gene RNA. In addition, the meroduplex may have one or more modifications or substitutions, such as nucleotide base, sugar, terminal cap structure, internucleotide linkage, or any combination of such modifications. Also provided are methods of decreasing expression of a target gene in a cell or in a subject to treat a disease related to altered expression of a target gene. 164-. (canceled)65. A method for reducing expression of a target gene in a cell , said method comprising:contacting a target gene expressing cell with a 19 to 30 base pair double-stranded ribonucleic acid, wherein said target gene expression is reduced as a consequence of contacting said cell with said double-stranded ribonucleic acid, said ribonucleic acid comprising(a) an A strand having a length of 15 to 30 nucleotides and a nucleotide sequence that is complementary to a nucleotide sequence in said target gene;(b) an S1 strand having a length of 5 to 25 nucleotides, wherein said Si strand anneals to said A strand thereby forming a first double-stranded region of 5 to 15 base pairs; and(c) an S2 strand having a length of 5 to 25 nucleotides, wherein said S2 strand anneals to said A strand thereby forming a second double-stranded region of 3 to 25 base pairs and wherein said annealed S2 strand is separated from said annealed S1 strand by a nick or a gap.66. The method of wherein said double-stranded ribonucleic acid has 0 claim 65 , 1 claim 65 , or 2 overhangs.67. The method of wherein said A strand has a length of 18 to 25 nucleotides.68. The method of wherein said A strand has a length of from 25 to 30 nucleotides.69. The method of wherein one ...

POLYMER-BASED NANOPARTICLES, RELATED FORMULATIONS METHODS, AND APPARATUS

This invention pertains to the field of biopolymer-loaded (where the biopolymer(s) are active pharmaceutical ingredient(s) (API(s)) polymer-based nanoparticles formulated, for example, for curative, therapeutic prophylactic and/or diagnostic applications. The polymer used to formulate the nanoparticles can be any biodegradable synthetic polymer or combination of polymers, including combinations of PLGA and PEG. Biopolymers used as active pharmaceutical ingredients (API) can include natural and unnatural nucleic acids such as DNA, RNA and LNA. Biopolymers used as active pharmaceutical ingredients (APIs) can also include neutral and positively charged nucleic acid mimics (NPNAM) such as for example, peptide nucleic acids, morpholinos, pyrrolidine-amide oligonucleotide mimics, morpholinoglycine oligonucleotides and methyl phosphonates and derivatives thereof. In some embodiments, the nanoparticles are loaded with both nucleic acids and NPNAMs as the APIs. Nanoparticles so formulated can be used in curative, therapeutic, prophylactic and/or diagnostic applications. Certain preferred nanoparticles, formulation methodologies, de-formulation methodologies and apparatus are also disclosed. 1. A method comprising: (i) the first solution comprises a first solvent; and', '(ii) the second solution comprises: (w) a neutral or positively charged nucleic acid mimic (NPNAM); (x) a polymer, and (y) a second solvent;, 'wherein, 'a) combining a first solution and a second solution at a junction under conditions suitable to produce nanoprecipitation in a post-junction fluid stream comprising post-junction fluid,'}b) forming a nanoparticle comprising the polymer and the NPNAM in the post-junction fluid stream.2. The method of claim 1 , wherein the polymer comprises a synthetic polymer.3. The method of claim 1 , wherein:(i) the first solution comprises water or an aqueous solution or buffer; and(ii) the second solution comprises: (w) a neutral or positively charged nucleic acid mimic ( ...

ANTISENSE OLIGONUCLEOTIDES FOR THE TREATMENT OF LEBER CONGENITAL AMAUROSIS

The present invention relates to the fields of medicine and immunology. In particular, it relates to novel antisense oligonucleotides that may be used in the treatment, prevention and/or delay of Leber congenital amaurosis. 1. A method for treating a CEP290 related disease or condition requiring modulating splicing of CEP290 , the method comprising administering to a subject in need thereof , an exon skipping antisense oligonucleotide that binds to and/or is complementary to a polynucleotide with the nucleotide sequence according to SEQ ID NO: 6 , SEQ ID NO: 7 , SEQ ID NO: 8 , or a part thereof.2. The method according to claim 1 , wherein said antisense oligonucleotide has a length from about 8 to about 128 nucleotides.3. The method according to claim 1 , wherein said antisense oligonucleotide comprises a sequence selected from the group consisting of SEQ ID NO: 10 claim 1 , SEQ ID NO: 11 claim 1 , and SEQ ID NO: 12.4. The method according to wherein said antisense oligonucleotide comprises a 2′-O alkyl phosphorothioate antisense oligonucleotide.5. The method according to claim 1 , wherein the 2′-O alkyl phosphorothioate antisense oligonucleotide is selected from the group consisting of 2′-O-methyl modified ribose (RNA) claim 1 , 2-O-ethyl modified ribose claim 1 , 2′-O-propyl modified ribose claim 1 , and/or substituted derivatives thereof.6. The method according to claim 1 , wherein the substituted derivatives are halogenated derivatives.7. The method according to claim 1 , wherein the disease or condition is Leber congenital amaurosis.8. A method for treating a CEP290 related disease or condition requiring modulating splicing of CEP290 claim 1 , the method comprising administering to a subject in need thereof claim 1 , a vector expressing an exon skipping antisense oligonucleotide when placed under conditions conducive to expression of the antisense oligonucleotide claim 1 , wherein said antisense oligonucleotide binds to and/or is complementary to a ...

COMPOSITIONS AND METHODS FOR TREATMENT OF CYSTIC FIBROSIS

Compositions and methods of genome engineering in vitro and in vivo are provided. In some embodiments, the compositions are triplex forming molecules that bind or hybridize to a target region sequence in the human cystic fibrosis transmembrane conductance regulator (CFTR) gene. Preferably the triplex forming molecules are peptide nucleic acids that include a Hoogsteen binding peptide nucleic acid (PNA) segment and a Watson-Crick binding PNA segment collectively totaling no more than 50 nucleobases in length, wherein the two segments can binid or hybridize to a target region in the CFTR gene having a polypurine sequences and induce strand invasion, displacement, and formation of a triple-stranded molecule among the two PNA segments and the target region's sequence. Methods of using the triplex forming molecules to treat cystic fibrosis are also provided. 1. A triplex forming composition comprising one or more oligonucleotides that the bind or hybridize to a target region sequence in the human cystic fibrosis transmembrane conductance regulator (CFTR) gene of cell comprising TTTCCTCT (SEQ ID NO:70) , TTTCCTCTATGGGTAAG (SEQ ID NO:71) , AGAGGAAA (SEQ ID NO:72) , CTTACCCATAGAGGAAA (SEQ ID NO:73) , AGAAGAGG (SEQ ID NO:74) , ATGCCAACTAGAAGAGG (SEQ ID NO:75) , CCTCTTCT (SEQ ID NO:76) , CCTCTTCTAGTTGGCAT (SEQ ID NO:77) , CTTTCCCTT (SEQ ID NO:78) , CTTTCCCTTGTATCTTTT (SEQ ID NO:79) , AAGGGAAAG (SEQ ID NO:80) , or AAAAGATAC AAGGGAAAG (SEQ ID NO:81).2. The triplex forming composition of comprising a triplex forming oligonucleotide substantially complementary to the target region sequence the can form a triple helix with double-stranded DNA at the target sequence based on the third strand binding code.4. The triplex forming composition of claim 3 , wherein the Hoogsteen binding segment comprises one or more chemically modified cytosines selected from the group consisting of pseudocytosine claim 3 , pseudoisocytosine claim 3 , and 5-methylcytosine.5. The triplex forming ...

CHIMERIC DOUBLE-STRANDED NUCLEIC ACID

A method of reducing the level of a transcription product in a cell comprising contacting with the cell a composition comprising a double-stranded nucleic acid complex comprising a first nucleic acid strand annealed to a second nucleic acid strand, wherein: (i) the first nucleic acid strand hybridizes to the transcription product and comprises (a) a region consisting of at least 4 consecutive nucleotides that are recognized by RNase H when the strand is hybridized to the transcription product, (b) one or more nucleotide analogs located on 5′ terminal side of the region, (c) one or more nucleotide analogs located on 3′ terminal side of the region and (d) a total number of nucleotides and nucleotide analogs ranging from 8 to 35 nucleotides and (ii) the second nucleic acid strand comprises (a) nucleotides and optionally nucleotide analogs and (b) at least 4 consecutive RNA nucleotides. 2. The pharmaceutical composition according to claim 1 , wherein the hairpin linker is hairpin loop nucleic acid which links the first nucleic acid and the second nucleic acid.3. The pharmaceutical composition according to claim 1 , wherein the first nucleic acid strand is further comprises (b) a 5′ wing region which comprises one or more nucleotide analogs or modified nucleotide analogs located 5′ to the at least 4 consecutive DNA nucleotides or modified DNA nucleotides that are recognized by RNase H; and/or (c) a 3′ wing region which comprises one or more nucleotide analogs or modified nucleotide analogs located 3′ to the at least 4 consecutive DNA nucleotides or modified DNA nucleotides that are recognized by RNase H.4. The pharmaceutical composition according to claim 1 , wherein the double stranded nucleic acid complex further comprises a third nucleic acid strand annealed to the second nucleic acid strand.5. The pharmaceutical composition according to claim 4 , wherein the third nucleic acid strand (i) comprises nucleotides and optionally nucleotide analogs and total number of the ...

NEUTRAL NUCLEIC ACID LIGANDS

The invention generally relates to isolated nucleic acid ligands that are neutral under physiological conditions. 1. A method for synthesizing a neutral nucleic acid ligand , the method comprising:providing a plurality of nucleosides; andperforming a chemical reaction to form neutral phosphate residues connecting the plurality of nucleosides, thereby generating a nucleic acid ligand that is neutral under normal physiological conditions in a mammalian body.2. The method of claim 1 , wherein the providing step comprises providing a nucleic acid ligand comprising the plurality of nucleosides connected by negatively charged phosphate residues; andwherein the chemical reaction comprises converting the negatively charged phosphate residues into neutral phosphate residues.3. The method of claim 2 , wherein converting comprises chemically modifying the phosphate residues.4. The method of claim 3 , wherein chemically modifying the phosphate residues comprises converting a phosphodiester bond into a phosphotriester bond.5. The method of claim 1 , wherein the chemical reaction comprises:reacting a 5′-protected nucleoside with tribenzyl pyrophosphate to produce a 3′-(benzyl phosphate) 5′-protected nucleoside;converting the 3′-(benzyl phosphate) 5′-protected nucleoside into a 3′-(benzyl phosphochloridate) 5′-protected nucleoside;reacting the 3′-(benzyl phosphochloridate) 5′-protected nucleoside with a 3′-O-acetylnucleside to form a 3′-O-acetylated posphotriesterified dinucleotide;deacetylating the 3′-O-acetylated posphotriesterified dinucleotide to form a phosphotriesterified oligonucleotide; andpreventing deblocking of the phosphotriesterified oligonucleotide to leave a neutral nucleic acid ligand.6. The method of claim 2 , wherein the nucleic acid ligand is a naturally occurring aptamer.7. The method of claim 1 , wherein the providing step comprises providing a plurality of nucleosides that are not covalently linked to each other.9. The method of claim 8 , wherein the 0- ...

Antisense oligonucleotides for the treatment of leber congenital amaurosis

The present invention relates to the fields of medicine and immunology. In particular, it relates to novel antisense oligonucleotides that may be used in the treatment, prevention and/or delay of Leber congenital amaurosis.

AN ENGINEERED MULTI-COMPONENT SYSTEM FOR IDENTIFICATION AND CHARACTERISATION OF T-CELL RECEPTORS AND T-CELL ANTIGENS

The present invention relates to A multicomponent system wherein a first component is an engineered antigen-presenting cell (eAPC) designated component A and a second component is a genetic donor vector, designated component C, for delivery of one or more ORFs encoding an analyte antigen-presenting complex (aAPX) and/or an analyte antigenic molecule (aAM), wherein component A 147.-. (canceled)48. A method of selecting a component of or output from an analyte engineered antigen-presenting cell T-cell receptor (eAPC:T) system , wherein the eAPC-T system comprises an analyte engineered antigen-presenting cell (eAPC) and an analyte cell (analyte TC) , wherein the eAPC is a cell that lacks endogenous expression of one or more of an antigen-presenting complex and an analyte antigenic molecule , wherein the eAPC comprises a genomic receiver site for integration of an open reading frame (ORF) encoding an analyte antigen and wherein the analyte TC expresses on its surface a T cell receptor (analyte TCR) , the method comprising:(a) detecting a reported signal response from the eAPC:T system, wherein the reported signal response is based on an interaction between the analyte antigen and the analyte TCR; and(b) selecting a component of or a output from the eAPC:T system based on the presence or absence of the reported signal response, wherein the component is selected from the eAPC and the analyte TC, and wherein the output is selected from an affinity reagent and a non-cell based particle (NCBP).50. The method of claim 49 , wherein step (a) comprises detecting an increase or decrease in (vi) or (vii).51. The method of claim 50 , wherein step (a) further comprises detecting an increase or decrease in one or more of (i)-(v).52. The method of clam of claim 49 , wherein step (a) comprises detecting an increase or decrease in (vii) claim 49 , and wherein (vii) is determined by detecting an increase or decrease in any of:(1) a secreted biomolecule;(2) a secreted chemical;(3) an ...

AN ENGINEERED MULTI-COMPONENT SYSTEM FOR IDENTIFICATION AND CHARACTERISATION OF T-CELL RECEPTORS AND T-CELL ANTIGENS

The present invention relates to A multicomponent system wherein a first component is an engineered antigen-presenting cell (eAPC) designated component A and a second component is a genetic donor vector, designated component C, for delivery of one or more ORFs encoding an analyte antigen-presenting complex (aAPX) and/or an analyte antigenic molecule (aAM), wherein component A a. Lacks endogenous surface expression of at least one family of aAPX and/or aAM and b. Contains at least two genomic receiver GO sites, designated component B and component D, each for integration of at least one ORF encoding at least one aAPX and/or aAM, and component C is matched to a component B, and wherein component C is designed to deliver c. A single ORF encoding at least one aAPX and/or aAM or d. Two or more ORF encoding at least one aAPX and/or aAM, wherein the genomic receiver sites B and D are synthetic constructs designed for re-combinase mediated exchange (RMCE). 147-. (canceled)48. A multicomponent system , comprising:as Component A, an engineered antigen presenting cell (eAPC), wherein the eAPC lacks endogenous surface expression of at least one family of antigen-presenting complex (aAPX) and/or an analyte antigenic molecule (aAM), and further comprises a single Component B,wherein Component B is a first genomic receiver site for integration of at least one open reading frame (ORF) encoding at least one aAPX and/or aAM, wherein Component B is a synthetic construct designed for recombinase mediated cassette exchange (RMCE); andas Component C, a first genetic donor vector for delivery of (i) a single ORF encoding at least one aAPX and/or aAM; or (ii) two or more ORFs encoding at least one aAPX and/or aAM, wherein Component C is matched to Component B.49. The multicomponent system of claim 48 , wherein Component A further comprises a Component D claim 48 , wherein Component D is (i) a second genomic receiver site for integration of at least one open reading frame (ORF) encoding at ...

COMPOSITIONS AND METHODS FOR DETECTING VIRAL NUCLEIC ACIDS

Described herein are compositions that may be used to detect viral nucleic acid. For example, these compositions may comprise a DNA-nanostructure, a capture oligonucleotide and a protector oligonucleotide, wherein the components are designed based on a duo-toehold-mediated displacement reaction (duo-TMDR) strategy. In this strategy, a first TMDR can switch off a Foster resonance energy transfer (FRET) process and a second TMDR can release the target viral nucleic acid and amplify the signal. Methods of using such compositions are also provided herein. 1. A composition for detecting a viral nucleic acid in a sample , the composition comprising:a DNA-nanostructure, a capture oligonucleotide and a protector oligonucleotide;wherein the DNA-nanostructure is operably linked to a fluorophore and the protector oligonucleotide is operably linked to a quencher or the DNA-nanostructure is operably linked to a quencher and the protector oligonucleotide is operably linked to a fluorophore; and wherein the quencher is capable of quenching the fluorescent light emitted from the fluorophore;wherein the protector oligonucleotide is capable of hybridizing to the DNA-nanostructure;wherein the viral nucleic acid is capable of displacing the protector oligonucleotide and hybridizing to the DNA-nanostructure; andwherein the capture oligonucleotide is capable of displacing the viral nucleic acid and hybridizing to the DNA-nanostructure but is not capable of displacing the protector oligonucleotide.2. The composition of claim 1 , wherein the DNA-nanostructure comprises at least one single stranded region.3. The composition of claim 2 , wherein the single stranded region comprises a nucleic acid sequence that comprises a first toehold domain claim 2 , a hybridization region and a second toehold domain.4. The composition of claim 3 , wherein the first toehold domain comprises a nucleic acid sequence that is complementary to a portion of the viral nucleic acid.5. The composition of claim 3 , ...

CRISPR Fluorescent Guide RNA (fgRNA) to Understanding gRNAs Expressed from Pol II Promotors

Provided herein are tools for understanding and engineering dynamics of synthetic genetic circuits which utilize CRISPR components. More particularly, methods, systems, and compositions for directing Cas9 activity using a fluorescent guide RNA (fgR-NA) which fluoresces in the presence of small molecules (e.g., DFHBI-IT) are described and illustrated in the present provisional application.

GENOME EDITING USING EFFECTOR OLIGONUCLEOTIDES FOR THERAPEUTIC TREATMENT

The invention provides compositions and methods of making and using effector oligonucleotides, including effector oligonucleotides with greater than one mismatch as compared to its target sequence. These effector oligonucleotides are useful for improving the efficiency of genomic editing as well as providing therapeutic benefits to individuals in need thereof. 146-. (canceled)47. An effector oligonucleotide comprising a sequence selected from the group consisting of SEQ ID NO:5 , SEQ ID NO:6 , SEQ ID NO:7 , SEQ ID NO:8 , SEQ ID NO:9 , SEQ ID NO:10 , SEQ ID NO:11 , SEQ ID NO:12 , SEQ ID NO:13 , SEQ ID NO:14 , SEQ ID NO:15 , SEQ ID NO:16 , SEQ ID NO:17 , SEQ ID NO:18 , SEQ ID NO:19 , SEQ ID NO:20 , SEQ ID NO:21 , SEQ ID NO:22 , SEQ ID NO:23 , SEQ ID NO:24 , SEQ ID NO:25 , SEQ ID NO:26 , SEQ ID NO:27 , SEQ ID NO:28 , SEQ ID NO:29 , SEQ ID NO:30 , SEQ ID NO:31 , SEQ ID NO:32 , SEQ ID NO:33 , SEQ ID NO:34 , SEQ ID NO:35 , SEQ ID NO:36 , and SEQ ID NO:37.48. The effector oligonucleotide of having the sequence selected from the group consisting of SEQ ID NO:5 claim 47 , SEQ ID NO:6 claim 47 , SEQ ID NO:7 claim 47 , SEQ ID NO:8 claim 47 , SEQ ID NO:9 claim 47 , SEQ ID NO:10 claim 47 , SEQ ID NO:11 claim 47 , SEQ ID NO:12 claim 47 , SEQ ID NO:13 claim 47 , SEQ ID NO:14 claim 47 , SEQ ID NO:15 claim 47 , and SEQ ID NO:16.49. The effector oligonucleotide of having the sequence selected from the group consisting of SEQ ID NO:5 claim 48 , SEQ ID NO:6 claim 48 , SEQ ID NO:7 claim 48 , SEQ ID NO:8 claim 48 , SEQ ID NO:9 claim 48 , SEQ ID NO:10 claim 48 , SEQ ID NO:11 claim 48 , SEQ ID NO:12 claim 48 , SEQ ID NO:15 claim 48 , and SEQ ID NO:16.50. The effector oligonucleotide of claim 47 , wherein the effector oligonucleotide is a non-naturally occurring oligonucleotide.51. A composition comprising the effector oligonucleotide according to .5253-. (canceled)54. The effector oligonucleotide of claim 47 , wherein the effector oligonucleotide comprises a mismatch in a human CCR5 ...

Method of treating inflammatory lung disease with suppressors of CpG oligonucleotides

The present disclosure relates to oligodeoxynucleotides that suppress an immune response. Methods are disclosed for inhibiting or treating inflammatory lung disease by administering a therapeutically effective amount of a suppressive oligodeoxynucleotide.

Recombinase mediated DNA therapies

Nucleoproteins comprising overlapping homologous DNA sequences coated with a recombinase are employed for introduction into cells to produce double D-loop structures. The sequences may be modified with various moieties which result in modification of DNA. Formation of the D-loops results in inhibition of replication and transcription, where the moieties can be employed for permanent scission or modification of the DNA. The methods and compositions can be used for investigating physiological processes, for producing animal models, and for inhibition of an undesirable phenotype in vivo.

Method for making synthetic oligonucleotides which bind specifically to target sites on duplex DNA molecules, by forming a colinear triplex, the synthetic oligonucleotides and methods of use

A method for making synthetic oligonucleotides which bind to target sequences in a duplex DNA forming colinear triplexes by binding to the major groove. The method includes scanning genomic duplex DNA and identifying nucleotide target sequences of greater than about 20 nucleotides having either about at least 65% purine bases or about at least 65% pyrimidine bases; and synthesizing synthetic oligonucleotides complementary to identified target sequences. The synthetic oligonucleotides have a G when the complementary location in the DNA duplex has a GC base pair and have a T when the complementary location in the DNA duplex has an AT base pair. The synthetic oligonucleotides are oriented 5' to 4' and bind parallel or 3' to 5' and bind anti-parallel to the about at least 65% purine strand.

HYDROXYMETHYL-MODIFIED GAMMA-PNA COMPOSITIONS AND METHODS OF USE THEREOF

Peptide nucleic acid (PNA) oligomers having one or more hydroxymethyl γ-substitutions, also referred to herein as “γPNA”, are provided. The hydroxymethyl γ-substitution preserves and amplifies the helical preorganization that is valuable for DNA duplex invasion by the oligomer. γPNA-containing triplex-forming molecules can be used in combination with a donor DNA fragment to facilitate genome modification in vitro and in vivo. 1. A peptide nucleic acid oligomer comprising a Hoogsteen binding peptide nucleic acid (PNA) segment and a Watson-Crick binding PNA segment collectively totaling no more than 50 PNA residues in length , wherein the two segments can bind or hybridize to a target region comprising a polypurine stretch in a cell's genome to induce strand invasion , displacement , and formation of a triple-stranded molecule among the two PNA segments and the polypurine stretch of the cell's genome ,wherein the Hoogsteen binding segment binds to the target duplex by Hoogsteen binding for a length of least five nucleobases,wherein the Watson-Crick binding segment binds to the target duplex by Watson-Crick binding for a length of least five nucleobases, and{'sup': 'ser', 'wherein two or more of the PNA residues have a hydroxymethyl-modification at the gamma position (“γPNA”).'}2. The peptide nucleic acid oligomer of claim 1 , wherein alternating residues in the Hoogsteen binding segment claim 1 , Watson-Crick binding segment claim 1 , or a combination thereof have a hydroxymethyl-modification at the gamma position (“γPNA”) and are unmodified at the gamma position claim 1 , respectively.3. The peptide nucleic acid oligomer of claim 2 , wherein alternating residues in the Hoogsteen binding portion only or in the Watson-Crick binding portion only have the hydroxymethyl-modification at the gamma position (“γPNA”) and unmodified at the gamma position claim 2 , respectively.4. The peptide nucleic acid oligomer of claim 3 , wherein all of the peptide nucleic acid residues in ...

Osteoarthritis biomarkers and uses thereof

The invention relates to the identification and selection of novel biomarkers and the identification and selection of novel biomarker combinations which are differentially expressed in osteoarthritis and/or in a particular stage of 6steoarthritis, as well as a means of selecting the novel biomarker combinations. The measurement of expression of the products of the biomarkers and combinations of biomarkers of the invention demonstrates particular advantage in one or more of the following: (a) diagnosing individuals as having arthritis, (b) differentiating between two stages of osteoarthritis (OA) and (c) diagnosing individuals as having a particular stage of osteoarthritis (OA). As would be understood, in order to measure the products of biomarkers of the invention, polynucleotides and proteins which specifically and/or selectively hybridize to the products of the biomarkers of the invention are also encompassed within the scope of the invention as are kits containing said polynucleotides and proteins for use in (a) diagnosing individuals as having arthritis, (b) differentiating between two stages of osteoarthritis (OA) and (c) diagnosing individuals as having a particular stage of osteoarthritis (OA). Further encompassed by the invention is the use of the polynucleotides and proteins which specifically and/or selectively hybridize to the product of the biomarkers of the invention to monitor disease progression in an individual and to monitor the efficacy of therapeutic regimens. The invention also provides for methods of using the products of the biomarkers of the invention in the identification of novel therapeutic targets for osteoarthritis. The invention also provides for methods of using the products of the biomarkers of the invention in the identification of compounds that bind and/or modulate the activity of the genes of the invention. The compounds identified via such methods are useful for the development of assays to study osteoarthritis and osteoarthritis ...

IL-17 homologous polypeptides and therapeutic uses thereof

METHOD FOR INHIBITING IL-22-INDUCED PAP1

Nucleic acids encoding human telomerase reverse transcriptase and related homologs

The invention provides compositions and methods related to human telomerase reverse transcriptase (hTRT), the catalytic protein subunit of human telomerase. The polynucleotides and polypeptides of the invention are useful for diagnosis, prognosis and treatment of human diseases, for changing the proliferative capacity of cells and organisms, and for identification and screening of compounds and treatments useful for treatment of diseases such as cancers.

Composition for inhibiting gene expression and uses thereof

Triple helix formation in oligonucleotide therapy

Oligonucleotides having tandem sequences of inverted polarity, i.e., oligonucleotides comprising regions of the formula: 3'-----5'--C--5'-----3' or 5'-----3'--C--3'-----5', wherein -C- symbolizes any method of coupling the nucleotide sequence of opposite polarity, are useful for forming an extended triple helix with a double-helical nucleotide duplex. Single or mixed motif oligomers may be used. The inverted polarity also stabilizes the single-strand oligonucleotides to exonuclease degradation.

Pyrimidine targeting hairpin triplex-forming oligonucleotides

Hairpin triplex-forming oligonucleotides that target pyrimidine nucleic acids are disclosed. The oligonucleotides of the invention are characterized by having a duplex-forming region, a triplex-forming region, and a linker region wherein one of the internucleoside linkages between the duplex-forming and triplex-forming region is a 5'-5' or 3'-3' linkage. The duplex-forming region is comprised of purine nucleosides and has a sequence substantially complementary to a pyridine region of a target nucleic acid. The triplex-forming region is comprised of pyrimidine nucleosides and is substantially complementary in the Watson-Crick sense to the duplex-forming region. The linker region is comprised of nucleotides or other moieties that link the duplex- and triplex-forming regions. In the absence of target, the hairpin triplex-forming oligonucleotide folds back upon itself, the duplex- and triplex-forming regions running in parallel. In the presence of target nucleic acids, the duplex-forming region binds to the target by Watson-Crick bonding, and the triplex-forming region by Hoogsteen bonding, forming a triplex. The disclosed oligonucleotides display increased stability and are useful for modulating gene expression.

Method for forming flow paths in blown multi-layer film

본 발명은 블로운 다층 필름에 공기 배출용 유로를 형성하기 위한 블로운 다층 필름의 유로 형성 방법을 개시한다. 상기 유로 형성 방법은, 블로운 다층 필름에 유로를 형성하는 블로운 다층 필름의 유로 형성 방법에 있어서, 다층 필름의 한쪽 면을 예열하여 다층 필름을 연화시키는 예열 단계와, 예열된 다층 필름을 온도 조절 가능하고 입구와 출구를 구비하는 폐쇄 챔버 내로 이송하는 단계와, 상기 챔버 내에서, 표면 온도의 조절이 가능한 엠보싱 롤러 및 이 엠보싱 롤러와 마주한 고무 롤러 사이의 닙을 통과시켜 상기 다층 필름이 엠보싱되게 함으로써, 상기 다층 필름에 복수의 유로를 형성하는 유로 형성 단계를 포함하며, 상기 유로 형성 단계는 다층 필름이 엠보싱 롤러에 안착되는 안착 단계와, 상기 엠보싱 롤러에 형성된 조각 홀에 상응하는 필름의 일부가 고무 롤러에 의하여 조각 홀 내로 압입되어 유로가 형성되는 유로 형성 단계와, 형성된 유로가 상기 엠보싱 롤러의 내부에서 순환되는 공기에 의해 냉각되어 일부가 수축되는 냉각,수축 단계와, 유로가 형성된 다층 필름과 엠보싱 롤러가 서로 분리되는 분리 단계로 이루어지고, 이들 단계는 연속적으로 진행되는 것을 특징으로 한다. The present invention discloses a flow path forming method of a blown multilayer film for forming an air discharge flow path in the blown multilayer film. The flow path forming method includes a flow path forming method of a blown multilayer film in which a flow path is formed in a blown multilayer film, the preheating step of preheating one side of the multilayer film to soften the multilayer film, and temperature control of the preheated multilayer film. Transfer into a closed chamber capable of having an inlet and an outlet, and within the chamber, an embossing roller capable of controlling the surface temperature and a nip between the rubber roller facing the embossing roller so that the multilayer film is embossed And a flow path forming step of forming a plurality of flow paths in the multilayer film, wherein the flow path forming step includes a seating step in which the multilayer film is seated on the embossing roller, and a part of the film corresponding to the piece hole formed in the embossing roller is rubber. A flow path forming step of forming a flow path by press-fitting into the engraving hole by a roller; Cooling and contraction step of cooling by the air circulated inside the bossing roller, the contraction part is contracted, and the separation step of separating the multi-layer film and the embossing roller is formed with a flow path, these steps are ...

Method of influencing proloferative status of cells by means of specific nucleotide sequences of g-chain of human telomeric dna

FIELD: medicine. SUBSTANCE: invention relates to field of biotechnology, namely to method of influencing proliferative status of cells. Claimed invention can be used in medicine, in immunology, in gerontology and cosmetology. Method includes introduction in medium, which surrounds cells, and further penetration into them of specific nucleotide sequences of single-stranded overhangs of G-chain of human telomeric DNA in final concentration, which does not exceed 30 mcM. Said sequences differ in variants of telomeric DNA repeats and triplet endings. EFFECT: claimed invention makes it possible to control time of beginning of certain phases of cell cycle and its overall duration. 8 cl, 8 dwg, 4 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (51) МПК C12Q 1/68 (13) 2 550 267 C2 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ (21)(22) Заявка: ИЗОБРЕТЕНИЯ К ПАТЕНТУ 2012153541/10, 12.12.2012 (24) Дата начала отсчета срока действия патента: 12.12.2012 (72) Автор(ы): Чирясова Елена Андреевна (RU) (73) Патентообладатель(и): Чирясова Елена Андреевна (RU) (43) Дата публикации заявки: 27.06.2013 Бюл. № 18 R U Приоритет(ы): (22) Дата подачи заявки: 12.12.2012 (45) Опубликовано: 10.05.2015 Бюл. № 13 2 5 5 0 2 6 7 R U Адрес для переписки: 142714, Московская обл.,Ленинский район,пос.Молоково Ново-Молоковский бульвар,19,кв.69 Чирясовой Елене Андреевне (54) СПОСОБ ВОЗДЕЙСТВИЯ НА ПРОЛИФЕРАТИВНЫЙ СТАТУС КЛЕТОК С ПОМОЩЬЮ СПЕЦИФИЧЕСКИХ НУКЛЕОТИДНЫХ ПОСЛЕДОВАТЕЛЬНОСТЕЙ G-ЦЕПИ ТЕЛОМЕРНОЙ ДНК ЧЕЛОВЕКА (57) Реферат: Изобретение относится к области оверхенгов G-цепи теломерной ДНК человека в биотехнологии, а именно к способу воздействия конечной концентрации, не превышающей 30 на пролиферативный статус клеток. мкМ. Указанные последовательности Предложенное изобретение может быть различаются вариациями теломерного повтора использовано в медицине в области лечения ДНК и триплетными окончаниями. онкологических заболеваний, в иммунологии, в Предложенное изобретение позволяет ...

IL-17 and IL-17R homologous polypeptides and therapeutic uses thereof

The present invention is directed to novel polypeptides and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention.

High affinity nucleic acid ligands of complement system proteins

Methods are described for the identification and preparation of high-affinity Nucleic Acid Ligands to Complement System Proteins. Methods are described for the identification and preparation of high affinity Nucleic Acid Ligands to Complement System Proteins C1q, C3 and C5. Included in the invention are specific RNA ligands to C1q, C3 and C5 identified by the SELEX method.

Increasing the proliferative capacity of cells using telomerase reverse transcriptase

The invention provides compositions and methods related to human telomerase reverse transcriptase (hTRT), the catalytic protein subunit of human telomerase. The polynucleotides and polypeptides of the invention are useful for diagnosis, prognosis and treatment of human diseases, for changing the proliferative capacity of cells and organisms, and for identification and screening of compounds and treatments useful for treatment of diseases such as cancers.

Telomerase

The present invention is directed to telomerase nucleic acids and amino acids. In particular, the present invention is directed to nucleic acid and amino acid sequences encoding various telomerase protein subunits and motifs, including the 123 kDa and 43 kDa telomerase protein subunits of Euplotes aediculatus , and related sequences from Schizosaccharomyces, Saccharomyces sequences, and human telomerase. The present invention is also directed to polypeptides comprising these telomerase protein subunits, as well as functional polypeptides and ribonucleoproteins that contain these subunits.

Method for detecting polynucleotides encoding telomerase

The present invention is directed to novel telomerase nucleic acids and amino acids. In particular, the present invention is directed to nucleic acid and amino acid sequences encoding various telomerase protein subunits and motifs, including the 123 kDa and 43 kDa telomerase protein subunits of Euplotes aediculatus , and related sequences from Schizosaccharomyces, Saccharomyces sequences, and human telomerase. The present invention is also directed to polypeptides comprising these telomerase protein subunits, as well as functional polypeptides and ribonucleoproteins that contain these subunits.

Telomerase

The present invention is directed to novel telomerase nucleic acids and amino acids. In particular, the present invention is directed to nucleic acid and amino acid sequences encoding various telomerase protein subunits and motifs, including the 123 kDa and 43 kDa telomerase protein subunits of Euplotes aediculatus, and related sequences from Schizosaccharomyces, Saccharomyces sequences, and human telomerase. The present invention is also directed to polypeptides comprising these telomerase protein subunits, as well as functional polypeptides and ribonucleoproteins that contain these subunits.

Human telomerase catalytic subunit

Promoter for telomerase reverse transcriptase

The invention provides compositions and methods related to human telomerase reverse transcriptase (hTRT), the catalytic protein subunit of human telomerase. The polynucleotides and polypeptides of the invention are useful for diagnosis, prognosis and treatment of humana diseases, for changing the proliferative capacity of cells and organisms, and for identification and screening of compounds and treatments useful for treatment of diseases such as cancers.

Human telomerase catalytic subunit: diagnostic and therapeutic methods

The invention provides compositions and methods related to human telomerase reverse transcriptase (hTRT), the catalytic protein subunit of human telomerase. The polynucleotides and polypeptides of the invention are useful for diagnosis, prognosis, and treatment of human diseases, for changing the proliferative capacity of cells and organisms, and for identification and screening of compounds and treatments useful for treatment of diseases such as cancers.

Treating cancer using a telomerase vaccine

The invention provides compositions and methods related to human telomerase reverse transcriptase (hTRT), the catalytic protein subunit of human telomerase. The polynucleotides and polypeptides of the invention are useful for diagnosis, prognosis and treatment of human diseases, for changing the proliferative capacity of cells and organisms, and for identification and screening of compounds and treatments useful for treatment of diseases such as cancers.

Human telomerase reverse transcriptase polypeptides

The invention provides compositions and methods related to human telomerase reverse transcriptase (hTRT), the catalytic protein subunit of human telomerase. The polynucleotides and polypeptides of the invention are useful for diagnosis, prognosis and treatment of human diseases, for changing the proliferative capacity of cells and organisms, and for identification and screening of compounds and treatments useful for treatment of diseases such as cancers.

Vaccine containing the catalytic subunit of telomerase for treating cancer

The invention provides compositions and methods related to human telomerase reverse transcriptase (hTRT), the catalytic protein subunit of human telomerase. The polynucleotides and polypeptides of the invention are useful for diagnosis, prognosis and treatment of human diseases, for changing the proliferative capacity of cells and organisms, and for identification and screening of compounds and treatments useful for treatment of diseases such as cancers.

Compositions and methods for the diagnosis and treatment of tumor

The present invention is directed to compositions of matter useful for the diagnosis and treatment of tumor in mammals and to methods of using those compositions of matter for the same.

Peptide nucleic acids

A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker.

Peptide nucleic acids

A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker.

New peptide nucleic acids

(57)【要約】 ペプチド核酸として知られる新規のクラスの化合物は、対応するＤＮＡよりも強く相補的ｓｓＤＮＡおよびＲＮＡ鎖と結合する。ペプチド核酸は一般に、適当なリンカーを介してペプチド主鎖に結合している天然に生ずるＤＮＡ塩基等のリガンドを含む。

Mammalian telomerase

Nucleic acids comprising the RNA component of a mammalian telomerase are useful as pharmaceutical, therapeutic, and diagnostic reagents.

Methods for modulating atrx-dependent gene repression

Methods and compositions for modulation of the activity of alpha thalassemia/mental retardation syndrome X-linked (ATRX), e.g., modulation of DNA- ATRX or RNA-ATRX interactions, and methods for identifying and using compounds that modulate DNA-ATRX or RNA-ATRX interactions, as well as the compounds themselves.

Hybrid oligonucleotides and uses thereof

Provided herein are hybrid oligonucleotides comprising a region that promotes cleavage of a nucleic acid and a region that protects a nucleic acid from exonuclease activity. Such hybrid oligonucleotides are useful for modulating the expression of genes. Related compositions and methods are also provided. In some embodiments, methods are provided for treating a disease, such as by administering a hybrid oligonucleotide.

Telomerase catalytic subunit

The invention provides compositions and methods related to telomerase reverse transcriptase, the catalytic protein subunit of human telomerase. The polynucleotides and polypeptides of the invention are useful for diagnosis, prognosis and treatment of human diseases, for changing the proliferative capacity of cells and organisms, and for identification and screening of compounds and treatments useful for treatment of diseases such as cancers.

Compositions and methods for inhibiting expression of anti-apoptotic genes

The present invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of an anti-apoptotic gene, comprising an antisense strand having a nucleotide sequence which is less that 25 nucleotides in length and which is substantially complementary to at least a part of an apoptotic gene, such as a Bcl gene. The invention also relates to a pharmaceutical composition comprising the dsRNA together with a pharmaceutically acceptable carrier; methods for treating diseases caused by the expression of an anti-apoptotic gene using the pharmaceutical composition; and methods for inhibiting the expression of an anti-apoptotic gene in a cell.

Compositions and methods for inhibiting expression of anti-apoptotic genes

The present invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of an anti-apoptotic gene, comprising a complementary RNA strand having a nucleotide sequence which is less that 25 nucleotides in length and which is substantially identical to at least a part of an apoptotic gene, such as a Bcl gene. The invention also relates to a pharmaceutical composition comprising the dsRNA together with a pharmaceutically acceptable carrier; methods for treating diseases caused by the expression of an anti-apoptotic gene using the pharmaceutical composition; and methods for inhibiting the expression of an anti-apoptotic gene in a cell.

Compositions and methods for inhibiting expression of anti-apoptotic genes

The present invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of an anti-apoptotic gene, comprising an antisense strand having a nucleotide sequence which is less that 25 nucleotides in length and which is substantially complementary to at least a part of an apoptotic gene, such as a Bcl gene. The invention also relates to a pharmaceutical composition comprising the dsRNA together with a pharmaceutically acceptable carrier; methods for treating diseases caused by the expression of an anti-apoptotic gene using the pharmaceutical composition; and methods for inhibiting the expression of an anti-apoptotic gene in a cell.

In vivo oligonucleotide generator, and methods of testing the binding affinity of triplex forming oligonucleotides derived therefrom

The present invention encompasses improved methods and materials for the delivering of antisense, triplex, and/or ribozyme oligonucleotides intracellularly, and RNA polymerase III-based constructs termed "oligonucleotide generators" to accomplish the delivery of oligonucleotides. Also encompassed by the present invention are methods for screening oligonucleotide sequences that are candidates for triplex formation.

Compositions and methods for the treatment and diagnosis of cardiovascular disease

The present invention relates to methods and compositions for the treatment and diagnosis of cardiovascular disease, including, but not limited to, atherosclerosis, ischemia/reperfusion, hypertension, restenosis, and arterial inflammation. Specifically, the present invention identifies and describes genes which are differentially expressed in cardiovascular disease states, relative to their expression in normal, or non-cardiovascular disease states, and/or in response to manipulations relevant to cardiovascular disease. Further, the present invention identifies and describes genes via the ability of their gene products to interact with gene products involved in cardiovascular disease. Still further, the present invention provides methods for the identification and therapeutic use of compounds as treatments of cardiovascular disease. Moreover, the present invention provides methods for the diagnostic monitoring of patients undergoing clinical evaluation for the treatment of cardiovascular disease, and for monitoring the efficacy of compounds in clinical trials. Additionally, the present invention describes methods for the diagnostic evaluation and prognosis of various cardiovascular diseases, and for the identification of subjects exhibiting a predisposition to such conditions.

Inhibiting gene expression in cells, useful for e.g. treating tumors, by introducing double-stranded complementary oligoRNA having unpaired terminal bases

Method for inhibiting expression of a target gene (A) in a cell by introducing at least one oligoribonucleotide (O1) that has a double-stranded (ds) structure consisting of at most 49 sequential nucleotide (nt) pairs, with at least part of one strand (S1) complementary with (A), and has, at least one end, a single-stranded (ss) segment of 1-4 nt. Independent claims are also included for: (a) O1 that target any of 140 gene sequences defined in the specification; and (b) kit comprising at least one O1, at least one other oligoribonucleotide (O2) with same size and structure as O1 but not necessarily having an ss-end, and/or interferon.

Nucleic acid-based treatment of diseases or conditions related to west nile virus infection

The present invention relates to nucleic acid molecules (e.g., ribozymes, DNAzymes, antisense oligonucleotides, triplex forming oligonucleotides, 2,5-A oligonucleotides, decoys) that modulate the expression and/or replication of West Nile Virus (WNV). The present invention also relates to chemical compositions, and methods of treatment of WNV infection and associated diseases, and conditions.

Compositions and methods for inhibiting expression of anti-apoptotic genes

The present invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of an anti-apoptotic gene, comprising an antisense strand having a nucleotide sequence which is less that 25 nucleotides in length and which is substantially complementary to at least a part of an apoptotic gene, such as a Bcl gene. The invention also relates to a pharmaceutical composition comprising the dsRNA together with a pharmaceutically acceptable carrier; methods for treating diseases caused by the expression of an anti-apoptotic gene using the pharmaceutical composition; and methods for inhibiting the expression of an anti-apoptotic gene in a cell.

Human telomerase catalytic subunit

본 발명은 인간의 텔로머라제 촉매성 단백질 서브유닛인 인간의 텔로머라제 역전사효소(hTRT)와 관련된 조성물 및 방법에 관한 것이다. 본 발명의 폴리뉴클레오티드와 폴리펩티드는 인간 질병을 확인, 예후 및 치료하는 용도, 세포와 유기체의 증식능을 변화시키는 용도 및 암과 같은 질병을 치료하는데 유용한 화합물과 치료제를 식별하고 선별하는 용도로 유용하다. The present invention relates to compositions and methods related to human telomerase reverse transcriptase (hTRT), which is a human telomerase catalytic protein subunit. Polynucleotides and polypeptides of the invention are useful for identifying, prognosticing, and treating human diseases, for changing the proliferative capacity of cells and organisms, and for identifying and selecting compounds and therapeutic agents useful for treating diseases such as cancer.

High affinity nucleic acid ligands of complement system proteins

Methods are described for the identification and preparation of high-affinity Nucleic Acid Ligands to Complement System Proteins. Methods are described for the identification and preparation of high affinity Nucleic Acid Ligands to Complement System Proteins C1q, C3 and C5. Included in the invention arc specific RNA ligands to C1q, C3 and C5 identified by the SELEX method.

Chimeric double-stranded nucleic acids

本发明公开了借助反义作用抑制靶基因表达的双链核酸复合物，和使用该双链核酸复合物的方法。一种用于减少细胞中转录产物水平的方法包括使组合物与细胞接触，所述组合物包含双链核酸复合物，所述双链核酸复合物包含与第二核酸链复性的第一核酸链，其中第一核酸链(i)包含核苷酸和任选地核苷酸类似物，并且第一核酸链中核苷酸和核苷酸类似物的总数是8至100，(ii)包含当第一核酸链与转录产物杂交时由RNA酶H识别的至少4个连续核苷酸，并且(iii)第一核酸链与转录产物杂交；和第二核酸链包含核苷酸和任选地核苷酸类似物。

Method for generating multivalent multispecific antibody-expressing cells by targeted integration of multiple expression cassettes in a defined tissue format

本文尤其报道了一种产生三价双特异性抗体的方法，所述方法包括以下步骤：培养包含编码所述三价双特异性抗体的脱氧核糖核酸的哺乳动物细胞，并从细胞或培养基中回收所述三价双特异性抗体，其中编码所述三价双特异性抗体的所述脱氧核糖核酸稳定地整合到所述哺乳动物细胞的基因组中并且在5'至3'方向上包含编码第一重链的第一表达盒、编码第一重链的第二表达盒、编码第一轻链的第三表达盒、编码第一轻链的第四表达盒、编码第二重链的第五表达盒、编码第一轻链或第二重链或第二轻链的第六表达盒和编码第二轻链的第七表达盒，其中所述第一重链从N末端至C末端包含第一重链可变结构域、CH1结构域、铰链区、CH2结构域、CH3结构域、肽接头、第二重链可变结构域和CL结构域，所述第二重链从N末端至C末端包含第一重链可变结构域、CH1结构域、铰链区、CH2结构域和CH3结构域，所述第一轻链从N末端至C末端包含第一轻链可变结构域和CH1结构域，且所述第二轻链从N末端至C末端包含第二轻链可变结构域和CL结构域，其中所述第二重链可变结构域和所述第一轻链可变结构域形成第一结合位点，且所述第一重链可变结构域和所述第二轻链可变结构域形成第二结合位点。

New peptide nucleic acids

Method of treating inflammatory lung disease with suppressors of CpG oligonucleotides

The present disclosure relates to oligodeoxynucleotides that suppress an immune response. Methods are disclosed for inhibiting or treating inflammatory lung disease by administering a therapeutically effective amount of a suppressive oligodeoxynucleotide.

Method of treating inflammatory lung disease with suppressors of CpG oligonucleotides

The present disclosure relates to oligodeoxynucleotides that suppress an immune response. Methods are disclosed for inhibiting or treating inflammatory lung disease by administering a therapeutically effective amount of a suppressive oligodeoxynucleotide.