259results about "Splicing alteration" patented technology

Aspects of the present disclosure relate to conjugates comprising a muscle targeting agent covalently linked to a molecular payload. In some embodiments, the muscle targeting agent specifically binds to an internalized cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in mRNA expressed from a mutant DMD allele.

The invention relates to guide polynucleotides and methods for targeting and editing a portion of the 5' UTR-encoding region of genes encoding VGSC alpha subunits (NaV) to abrogate or create an upstream open reading frame (uORF). The invention relates to guide polynucleotides and methods for targeting and editing a portion of the 5' splice acceptor site (SA) of an exon of a gene encoding a voltage-gated sodium channel (VGSC) alpha subunit (NaV). The invention also relates to use of the guide polynucleotides and methods for treating genetic disorders, in particular Dravet syndrome.

This invention relates to oligonucleotide compositions and methods for using the same. [Solution] In particular, this disclosure provides designed oligonucleotides, compositions thereof and methods of use. In some embodiments, this disclosure provides techniques useful for reducing transcript levels. In some embodiments, this disclosure provides techniques useful for modulating transcript splicing. In some embodiments, the techniques provided can alter the splicing of dystrophin (DMD) transcripts. In some embodiments, this disclosure provides methods for treating diseases such as Duchenne muscular dystrophy and Becker muscular dystrophy.

The present invention relates to a recombinant antisense oligonucleotide that targets CD33 mRNA and to a method of preparing a substantially pure population of edited eukaryotic cells comprising the steps of i) editing a population of eukaryotic cells by the use of base editors, (ii) treating the same population with antisense oligonucleotides according to the invention to transiently downregulate CD33 and iii) enriching the population of edited eukaryotic cells that is negative for CD33.

Antisense oligonucleotides for modulating UNC13A splicing (e.g., inhibiting the inclusion of UNC13A hidden exons in mature UNC13A mRNA), compositions comprising such antisense oligonucleotides, and methods of use are described. Also disclosed are pharmaceutical compositions comprising one or more antisense oligonucleotides, and methods for treating UNC13A-related diseases or diseases associated with TDP-43 dysfunction in a subject by administering the antisense oligonucleotides to that subject.

The present application provides an engineered circular RNA capable of recruiting adenosine deaminase acting on RNA (ADAR; arRNA) and its application in treating Duchenne muscular dystrophy (DMD).

An isolated or purified AON for modifying pre-mRNA splicing in the Receptor for Advanced Glycation End-products (RAGE) to modulate splicing of the RAGE gene transcript or part thereof is provided.

Hereditary peripheral neuropathy, also known as Charcot-Marie-Tooth disease (CMT), is one of the most common genetic disorders of the nervous system, affecting approximately 1 in 2500 people. The present disclosure relates to a therapeutic strategy, including methods and compositions, for treating Charcot-Marie-Tooth disease (CMT) by targeting the pre-mRNA of PMP22 using antisense oligonucleotides (ASOs).

Disclosed are conjugates of an oligonucleotide and a peptide covalently bonded or linked to the oligonucleotide via a linker that target a human dystrophin gene, compositions including the same, and methods of use thereof.

We provide gene therapy for the treatment of muscular dystrophy, including but not limited to Duchenne muscular dystrophy (DMD). [Solution] This disclosure provides a recombinant adeno-associated virus (rAAV) comprising a nucleic acid molecule that delivers a nucleic acid encoding a U7-based snRNA, which is a nucleic acid that induces exon skipping for use in the treatment of muscular dystrophy, including but not limited to DMD, resulting from any mutation suitable for skipping exon 44 of the DMD gene (DMD exon 44), including but not limited to mutations involved in or affecting DMD exon 44.

HTT nucleic acid trans-splicing molecules are described, which include a coding domain containing one or more exons of HTT, a splice site, and a binding domain that binds to a target intron of HTT pre-mRNA. The HTT nucleic acid trans-splicing molecules described herein can also be used in combination with, for example, an MSH3-binding domain arranged in tandem with an HTT-binding domain, an MSH3 nucleic acid trans-splicing molecule, an MSH3 splice modulator, an antisense oligonucleotide or antisense RNA against either MSH3 or HTT, and an MSH3 or HTT microRNA (miRNA), as well as constructs encoding them. Compositions containing the nucleic acid trans-splicing molecules described herein also encompass compositions containing a combination of the nucleic acid trans-splicing molecule and an additional therapeutic agent (e.g., an MSH3 nucleic acid trans-splicing molecule, an MSH3 splice modulator, an antisense oligonucleotide or antisense RNA against either MSH3 or HTT). Nucleic acid trans-splicing molecules and compositions containing them can be used alone or in combination with additional therapeutic agents in methods for treating Huntington's disease (HD). Also described herein are nucleic acid trans-splicing molecules for use alone or in combination with additional therapeutic agents in the treatment of HD or in the preparation of a medicament for treating HD. Also included herein are MSH3 nucleic acid trans-splicing molecules, MSH3 splice modulators, and MSH3 miRNAs, and constructs encoding them, which may be used alone or in combination and / or in combination with additional therapeutic agents to treat a nucleotide repeat disorder (e.g., HD) or in the preparation of a medicament for treating a nucleotide repeat disorder (e.g., HD).

Described herein in various embodiments are compositions comprising (a) a cyclic peptide; and (b) an antisense compound, wherein the antisense compound targets exon 44 of the DMD gene in a pre-mRNA sequence.

The application provides an antisense oligonucleotide Jag-i9 ASO and application thereof, relates to the technical field of biological medicine, and the antisense oligonucleotide Jag-i9 ASO has the sequence of 5'-ACTGGGCCCTGCACCTGA-3'. By providing the antisense oligonucleotide of a specific sequence, the binding site of target heterogeneous ribonucleoprotein K and the Jag2 gene is targeted, the expression of the pro-inflammatory Jag2 subtype is inhibited, the Jag2 gene splicing site can be accurately targeted, the heterogeneous ribonucleoprotein K binding function is specifically blocked, a targeted intervention means is provided for the treatment of myocardial ischemia-reperfusion injury, the generation of the pro-inflammatory subtype is inhibited by efficiently and accurately regulating the alternative splicing of a specific gene, myocardial cell apoptosis and inflammatory response are reduced, myocardial function is improved, and a new approach is provided for the prevention and treatment of myocardial ischemia-reperfusion injury, the treatment effect is improved, and the advantages of reducing side effects are achieved.

Disclosed herein are CRISPR-free compositions and methods for producing chimeric RNA molecules via trans-splicing, and methods for treating and / or preventing genetic diseases or disorders using the chimeric RNA molecules produced via trans-splicing. Disclosed herein are nucleic acid molecules comprising exogenous RNA to be trans-spliced ​​into a target endogenous pre-mRNA, a 5' hemi-intron, one or more RNA targeting motifs, and one or more RNA structures.

Recombinant polynucleotides and vectors containing an engineered (artificial) exon-intron-exon gene structure in a transgene are provided, which undergoes splicing when it is expressed in a target cell.

This invention relates to the finding that novel splice switching oligonucleotides can correct splicing mutations. Moreover, the invention relates to using the novel splice switching oligonucleotides to correct a 1811+1.6kb G>T (c. 1679+1643G>T). 1811+1.6kb A>G (c. 1679+1634A>G), 1811+1.6kb T>A (c. 1679+1650T>A), or W1282X (c.3846G>A) mutation in a pre-mRNA produced from the human CFTR gene and methods of using the same for treatment of cystic fibrosis (CF) in a subject.

The disclosure provides methods, compounds (molecules) and / or compositions for the treatment and / or prevention of diseases and / or conditions caused or contributed to by TAR DNA-binding protein 43 (TDP-43) dependent mis-splicing of its downstream target genes.

An isolated or purified antisense oligomer for modifying pre-mRNA splicing in the CNOT3 gene transcript or part thereof.

In particular, the present disclosure provides various techniques involving chiral controlled oligonucleotide compositions and techniques for making and using such oligonucleotide compositions. In some embodiments, the present disclosure provides techniques useful for preventing or treating various conditions, disorders or diseases, such as Duchenne muscular dystrophy.

The present invention relates to a mutated transcription factor EB (TFEB) protein that loses the native exon 3. This protein is referred to herein as "TFEB-ex3" or "ex3-TFEB". The invention also relates to polynucleotides encoding such muteins; a vector comprising the polynucleotide; and a biomolecular means for removing TFEB exon 3 in a patient in need thereof. The invention also relates to a pharmaceutical composition comprising the above, for use in the treatment and / or prevention of lysosomal storage diseases and conditions characterized by lysosomal dysfunction.

Provided are splice-modulating antisense oligonucleotides (ASOs) that target a terminal stem loop structure at the 3' end of intron 15 (TSL-3-15) of a Factor VIII (F8) pre-mRNA. Also provided are compositions comprising the splice-modulating ASOs. In some embodiments, the compositions are formulated for administration to a subject. Methods of treating Hemophilia A (HA) in a subject in need thereof are also provided. In certain embodiments, the subject exhibits aberrant splicing of Factor VIII (F8) exon 16, and the methods comprise administering to the subject a therapeutically effective amount of a composition of the present disclosure.

The present invention relates to compositions, methods and kits for treating or preventing the effects of smoke exposure. In particular, these compositions, methods and kits are particularly suitable for, but not limited to, treatment or prevention of acute or chronic smoke exposure. In one aspect, the invention provides a method of treating or preventing obstructive pulmonary disease associated with or caused by smoke exposure in a subject in need thereof, the method comprising administering to the subject an antisense oligonucleotide (AON) that promotes the production of endogenous soluble RAGE, thereby treating or preventing obstructive pulmonary disease associated with or caused by exposure to smoke in the subject.

The present invention relates to agents that increase the amount of a protein comprising a mutated RS domain amino acid sequence in the nucleus of a cell and / or decreases the amount of the same protein in the cytoplasm of said cell, for use in the prevention or treatment of a disease or condition that is related to the cytoplasmic mislocalization and / or the formation of granules and / or an aberrant splicing activity of the protein comprising the mutated RS domain amino acid sequence. In particular, the protein comprising a mutated RS domain amino acid sequence is RBM20 or an ortholog thereof, and / or the nuclear transporter protein is transportin 3 (TNPO3) or an ortholog thereof. Preferably, the disease or condition is myopathy, in particular dilated cardiomyopathy (DCM). The present invention further relates to a method for identifying suitable agents used to increase the amount of a protein comprising a mutated RS domain amino acid sequence in the nucleus of a cell and / or to decrease the amount of the same protein in the cytoplasm of said cell.

The present invention relates to a modified U1 snRNA configured to rescue exon skipping in a mutant ABCA4 gene. In one aspect of the invention, there is provided a modified U1 small nuclear RNA (snRNA) configured to retain exon 40 in a mature mRNA transcript of a mutant ABCA4 gene comprising a mutation that induces exon 40 skipping wherein the mutation is located between 3 base pairs upstream and 8 base pairs downstream of a donor splice site of exon 40, wherein the modification comprises replacing a portion of the single-stranded nucleotide sequence of the 5'region of the wild-type U1 snRNA with a single-stranded binding nucleotide sequence capable of hybridizing to a target sequence present on the precursor mRNA transcript of the mutant ABCA4 gene, and wherein the target sequence is located in a region between 13 base pairs upstream and 15 base pairs downstream of the donor splice site of exon 40. In another aspect, there is provided a nucleic acid construct comprising a polynucleotide sequence encoding a modified U1 snRNA as described herein.

Compositions and methods for reducing complement activation by introducing one or more modifications into intracellular complement component 3 (C3) polynucleotides. In certain embodiments, the disclosure features a base editor system (e.g., a fusion protein or complex comprising a programmable DNA-binding protein, a nucleic acid base editor, and a gRNA) for modifying a C3 polynucleotide, wherein the modification is associated with reduced expression and / or reduced activity of the C3 polypeptide encoded by the polynucleotide.

In the present description, provided are an antisense oligomer that enables simultaneous skipping of a plurality of exons in a target pre-mRNA and a medicinal composition comprising the oligomer. In the present description, also provided is an antisense oligomer enabling simultaneous skipping of two or more exons, said exons being consecutive in numerical order, from a target pre-mRNA, a pharmaceutically acceptable salt thereof or a hydrate of the same, wherein the antisense oligomer contains a base sequence that is complementary to the base sequence of a region containing the vicinity of a donor of any intron in the target pre-mRNA or a region containing the vicinity of an acceptor of any intron in the target pre-mRNA or a partial base sequence thereof.

The present invention relates to recombinant adeno-associated virus (rAAV) delivery of polynucleotides for treating Duchenne Muscular Dystrophy resulting from the duplication of DMD exon 2. The invention provides rAAV products and methods of using the rAAV in the treatment of Duchenne Muscular Dystrophy.

Described herein are compounds and methods that can be used to treat a disease or condition by increasing the SYNGAP1 protein.

Antisense oligonucleotides for altering the splicing pattern of progranulin, and their use in the treatment of neurological disorders. The antisense oligonucleotides are modified to better increase up-regulation or expression restoration of the Exon1-Exon2 progranulin splice variant in cells.