58 results about "Exon skipping" patented technology

Disclosed herein are antibody oligonucleotide conjugates and pharmaceutical compositions that induce an alteration in an incorrectly spliced dystrophin mRNA transcript to induce exon 44 skipping. Also described herein include methods for treating muscle dystrophy including Duchenne muscular dystrophy that comprises administering antibody oligonucleotide conjugates or a pharmaceutical composition that induces alteration in an incorrectly spliced dystrophin mRNA transcript to induce exon 44 skipping.

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.

The present invention provides a mesenchymal stem cell having blood compatibility, and a preparation method and use thereof, the mesenchymal stem cell inducing exon skipping of an exon 5 by performing gene modification on the exon 5 of an F3 gene, thereby increasing the expression of a selective splicing tissue factor (asTF), and improving the blood compatibility of the mesenchymal stem cell. The present invention relates to a method for inhibiting thrombosis by reducing or inhibiting the expression or activity level of a full-length tissue factor (flTF), which is a blood coagulation promoter, and thereby inhibiting thrombosis.

The present application relates to the technical field of gene mutation detection, and particularly relates to a system, method and application for detecting exon skipping mutation.The present application constructs a self-catalytic system based on specific double recognition induction of CRISPR-Cas12a, which is used for sensitive and reliable detection of MET 14 exon skipping mutation of lung cancer patients.The system can effectively release the fluorescence signal through the Cas12a auxiliary cutting, and further realize signal amplification through the self-catalytic mechanism.The present application can solve the technical problems of the existing exon skipping mutation detection system, such as complex detection process, long time consumption, and unsatisfactory detection accuracy.The detection system of the present application has high sensitivity, stability and good reproducibility, and the method has low cost, simple operation, short detection period, good specificity, and low false positive rate and false negative rate.The present application is suitable for clinical sample determination and has an ideal application prospect.

This invention provides a drug that efficiently skips the 50th exon of the human dystrophin gene. [Solution] An antisense oligomer or a pharmaceutically acceptable salt thereof or a hydrate thereof that induces skipping of the 50th exon of the human dystrophin gene is provided.

Disclosed herein are oligonucleotide conjugates and pharmaceutical compositions for inducing multi-exon skipping. In some instances, also disclosed herein are methods of treating a muscular dystrophy, including treating Duchenne muscular dystrophy or Becker muscular dystrophy.

Antisense polynucleotides and their use in pharmaceutical compositions to induce exon skipping in targeted exons of the gamma sarcoglycan gene are provided, along with methods of preventing or treating dystrophic diseases such as Limb-Girdle Muscular Dystrophy.

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.

Antisense oligomer conjugates complementary to a selected target site in the human dystrophin gene for inducing exon 45 skipping are described.

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 application provides a method of inducing precursor mRNA exon skipping in a host cell comprising introducing into the host cell a deaminase recruitment RNA (dRNA) or a construct comprising a nucleic acid encoding the dRNA wherein the dRNA is a circular RNA (circRNA) or forms a circular RNA in the host cell.

Disclosed herein are antibody oligonucleotide conjugates and pharmaceutical compositions that induce an alteration in an incorrectly spliced dystrophin mRNA transcript to induce exon 44 skipping. Also described herein include methods for treating muscle dystrophy including Duchenne muscular dystrophy that comprises administering antibody oligonucleotide conjugates or a pharmaceutical composition that induces alteration in an incorrectly spliced dystrophin mRNA transcript to induce exon 44 skipping.

Among other things, the present disclosure provides oligonucleotide compositions and methods thereof. In some embodiments, oligonucleotides comprise various chemical modifications of sugars, nucleobases, and / or mtemucleotidic linkages and patterns thereof and are useful for exon skipping. In some embodiments, the present disclosure provides technologies useful for skipping exon 45 of dystrophin (DMD) transcripts. In some embodiments, the present disclosure provides technologies useful for modulating DMD transcript splicing. In some embodiments, the present disclosure provides methods for preventing or treating conditions, disorders or diseases including Duchenne muscular dystrophy.

The disclosure relates to the field of chronic pain and the treatment thereof. The disclosure involves antisense oligonucleotides and the use thereof in pre-mRNA and mRNA modulation, in one aspect related to RNA editing using endogenous ADAR enzymes, in targeting an adenosine in a (pre-) mRNA for human Nav1.7, preferably to change from a lysine residue to an arginine residue in the protein at position 1406 (K1406R), thereby impairing the ability of the Nav1.7 protein to act as a sodium ion channel. In another aspect the disclosure relates to exon skipping wherein antisense oligonucleotides are used to induce skipping of exon 23 in the generation of human SCN9A mRNA thereby generating a shortened Nav1.7 protein with an impaired ability to act as a sodium ion channel. The disclosure relates to methods and means to alter the Nav1.7 protein in cells of the peripheral nervous system, preferably large nociceptor cells (type Aα / Aβ), to provide a treatment of chronic pain.

The present invention provides a novel linkage-type antisense oligomer that induces exon skipping by targeting base sequences at two different sites in the same exon of the dystrophin gene, and a therapeutic agent for muscular dystrophy comprising the oligomer.SOLUTION: It has been found that an antisense oligomer obtained by linking oligomers targeting two different sites of exon 45 of the human dystrophin gene can induce skipping of the exon.SELECTED DRAWING: None

Compositions and methods for treating diseases and conditions mediated by the high affinity IgE receptor (FcεRI) are provided. Also provided are antisense oligomers for modulating splicing of mRNA encoding a MS4A6A protein, optionally in addition to antisense oligomers for modulating splicing of mRNA encoding the FcεRIβ protein, thereby down-regulating cell-surface expression of FcεRI, and uses of the antisense oligomers for inhibiting mast cell degranulation, cytokine release, migration, and proliferation; for inhibiting anaphylaxis reactions in individuals, for treating allergic conditions in individuals, for reducing the incidence of allergic reactions in individuals, for treating individuals at risk of developing anaphylactic reactions, and for treating mast cell-related diseases in individuals.

Provided are novel antisense oligonucleotides that promote exon 14 skipping in the EZH2 gene, and their use in the treatment of cancer and other diseases.

The present invention provides a tau exon 10 skipping-promoting antisense oligonucleotide containing at least one 2′-O, 4′-C-ethylene-bridged nucleic acid, and a nucleotide sequence complementary to a sequence consisting of at least 10 continuous nucleotides in a region consisting of the nucleotide sequence shown in SEQ ID NO: 44 in exon 10 of a tau mRNA precursor. In addition, the present invention provides a tau exon 10 skipping-suppressing antisense oligonucleotide containing at least one 2′-O, 4′-C-ethylene-bridged nucleic acid, and a nucleotide sequence complementary to a sequence consisting of at least 10 continuous nucleotides in a region consisting of the nucleotide sequence shown in SEQ ID NO: 45 in intron 10 of a tau mRNA precursor.

This disclosure provides, in particular, oligonucleotide compositions and methods thereof. In some embodiments, the oligonucleotides comprise various chemical modifications of sugars, nucleobases, and / or internucleotide bonds and their patterns, and are available for exon skipping. In some embodiments, this disclosure provides techniques for use with exon 51 of a jumping dystrophin (DMD) transcript. In some embodiments, this disclosure provides techniques for modulating DMD transcript splicing. In some embodiments, this disclosure provides methods for preventing or treating conditions, disorders, or diseases including Duchenne muscular dystrophy.

Aspects of the present disclosure relate to conjugates, and other aspects relate to formulations (e.g., aqueous, lyophilized forms) comprising such conjugates (e.g., each conjugate represented by the exemplary formula below) comprising a phosphorodiamidate morpholino oligomer (e.g., useful for targeting DMD) covalently linked to an antibody (e.g., an anti-TfR1 antibody). Also provided is the use of these formulations for treating subjects with a mutated DMD allele associated with Duchenne muscular dystrophy. JPEG2026503873000028.jpg63163

The process of inducing pre-mRNA splicing was disclosed. CD33 Novel antisense oligonucleotides that skip exon 2 in genes and their potential applications in treating neurodegenerative diseases such as Alzheimer's disease.

To provide nucleic acid-polypeptide compositions and methods for inducing exon skipping.SOLUTION: Disclosed herein are molecules and pharmaceutical compositions that induce an insertion, deletion, duplication, or alteration in an incorrectly spliced mRNA transcript to induce exon skipping or exon inclusion. Also described herein are methods for treating a disease or disorder that comprises a molecule or a pharmaceutical composition that induces an insertion, deletion, duplication, or alteration in an incorrectly spliced mRNA transcript to induce exon skipping or exon inclusion.SELECTED DRAWING: Figure 3

The invention relates to the technical field of gene mutation detection, in particular to a system and method for detecting exon jump mutation and application. According to the technical scheme, an autocatalysis system based on CRISPR-Cas12a specificity dual recognition induction is constructed and is used for sensitively and reliably detecting MET 14 exon jump mutation of a lung cancer patient. According to the system, signal amplification can be further realized through an autocatalysis mechanism while Cas12a is effectively subjected to auxiliary cutting to release a fluorescence signal. According to the technical scheme, the technical problems that an exon jump mutation detection system in the prior art is complex in detection process, long in consumed time and not ideal in detection accuracy can be solved. The detection system disclosed by the invention shows the capabilities of high sensitivity, stability and good reproducibility, and the method is low in cost, simple and convenient to operate, short in detection period, good in specificity and low in false positive rate and false negative rate. The scheme is suitable for clinical sample determination and the like, and has ideal popularization and application prospects.

Novel conjugates of antisense oligonucleotides and cell-penetrating peptides that induce exon-2 skipping during pre-mRNA splicing and their use in the treatment of neurodegenerative diseases such as Alzheimer's disease are disclosed.

Among other things, the present disclosure provides oligonucleotide compositions and methods thereof. In some embodiments, oligonucleotides comprise various chemical modifications of sugars, nucleobases, and / or internucleotidic linkages and patterns thereof and are usefill for exon skipping. In some embodiments, the present disclosure provides technologies useful for skipping cryptic exons of stathmin-2(STMN2) transcripts. In some embodiments, the present disclosure provides technologies useful for modulating STMN2 transcript splicing. In some embodiments, the present disclosure provides methods for preventing or treating conditions, disorders or diseases including neurodegenerative diseases, e.g,, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).

Disclosed herein are antibody oligonucleotide conjugates and pharmaceutical compositions that induce an alteration in an incorrectly spliced dystrophin mRNA transcript to induce exon 44 skipping. Also described herein include methods for treating muscle dystrophy including Duchenne muscular dystrophy that comprises administering antibody oligonucleotide conjugates or a pharmaceutical composition that induces alteration in an incorrectly spliced dystrophin mRNA transcript to induce exon 44 skipping.

The present disclosure concerns antisense oligonucleotides (ASO) binding to a target site on exon 23 of the pre-mRNA of SORL1. The present invention further concerns a composition comprising said ASO. The present invention further concerns an ASO for use as a medicament. The present invention further concerns an ASO for use in the prevention, treatment and / or alleviation of e.g. Alzheimer's Disease (AD). The present invention further concerns a method for mediating exon skipping of exon 23 in SORL1 transcripts, a method of determining the efficiency of ASO mediated SORL1 exon 23 skipping, a method for testing if a patient identified with a SORL1 mutation will benefit from treatment with an ASO mediating exon 23 skipping, and a method of producing an ASO suitable for treatment of a patient with Alzheimer's Disease.

The application discloses application of hnRNPL in preparation of glioma diagnosis, treatment and prognosis evaluation products, and belongs to the technical field of biological medicine. Through bioinformatics and clinical sample verification, it is confirmed that hnRNPL is significantly highly expressed in glioma tissues, and the expression level thereof is negatively correlated with the total survival period of patients, and hnRNPL has the function of promoting the occurrence and development of glioma. Mechanism research shows that hnRNPL can be used as a key alternative splicing factor, which promotes the skipping of the second exon of SH3BGRL by combining with the CA-rich sequence on the SH3BGRL pre-mRNA, thereby generating functional SH3BGRL protein, and driving the proliferation, migration and invasion of glioma cells. Based on this, hnRNPL can be used as a molecular marker for the diagnosis and prognosis evaluation of glioma, and an inhibitor targeting hnRNPL can effectively inhibit the malignant progression of glioma.

This disclosure provides, in particular, oligonucleotide compositions and methods thereof. In some embodiments, the oligonucleotides comprise various chemical modifications of sugars, nucleobases, and / or internucleotide bonds and their patterns, and are available for exon skipping. In some embodiments, this disclosure provides techniques for use with exon 44 of a jumping dystrophin (DMD) transcript. In some embodiments, this disclosure provides techniques for modulating DMD transcript splicing. In some embodiments, this disclosure provides methods for preventing or treating conditions, disorders, or diseases including Duchenne muscular dystrophy.