122results about "Polymorphism uses" patented technology

The present invention relates to methods and compositions for editing an ABCA4 polynucleotide, e.g., an ABCA4 polynucleotide comprising a SNP associated with Stargardt Disease, type 1. The invention also relates to methods and compositions for treating or preventing Stargardt Disease, type 1, in a subject.

Compositions and methods for effecting base editing to correct mutations in the phenylalanine hydroxylase gene, thereby curing phenylketonuria, are disclosed.

The present disclosure relates generally to (CRISPR) RNA (crRNA) for the precision silencing of transcripts. In some embodiments, the crRNA are enriched for guanosine (G) nucleotides at key spacer positions, which is useful in enhancing the silencing efficacy of otherwise inefficient crRNA, thereby expanding the targeting spectrum of Cas13 endonucleases, e.g., Cas13b and Cas13d. In other embodiments, the crRNA comprise a spacer sequence having at least one nucleotide mismatch relative to the target RNA sequence, wherein the target RNA sequence is a wild-type transcript and / or a variant transcript (e.g., a transcript comprising a single nucleotide variant (SNV)). The present disclosure also provides RNA editing systems comprising the crRNA described herein in complex a Cas13 effector protein and a target RNA sequence, methods for the selective targeting of transcripts encoding proteins that are difficult to target, or are not amenable to pharmacological targeting, e.g., oncogenic fusion transcripts or oncogenic transcripts comprising single nucleotide variant(s), and methods for the design and selection of potent crRNA.

Disclosed herein are compositions comprising an oligonucleotide that inhibits the expression of MST1. The oligonucleotide includes a small interfering RNA (siRNA), as well as these compositions for use in methods of treating lung disorders

Described are compounds and methods useful for the treatment and investigation of diseases and disorders associated with expanded repeat-containing RNA molecules. In certain embodiments, compounds and methods useful for the modulation of ATXN-3 pre-mRNA are described. In certain embodiments, compounds and methods useful for the modulation of ATN-1 mRNA are described.

CRISPR / Cas-related compositions and methods for treatment of Usher Syndrome and / or Retinitis Pigmentosa are disclosed herein.

The present invention relates to nucleic acid molecules for allele-specific editing of the ELANE gene, vectors containing the nucleic acid molecules, compositions containing the nucleic acid molecules or the vectors, methods for allele-specific editing of the ELANE gene in vitro in biological material containing genetic material encoding the ELANE gene, and methods for preventing, treating and / or testing diseases in organisms.

Compositions include CRISPR RNAs, guide RNAs, and nucleic acid molecules encoding the same. Vectors and host cells comprising the nucleic acid molecules are also provided. Further provided are RNA-guided nuclease (RGN) systems for cleaving a mutHTT allele, wherein the RGN system comprises an RNA-guided nuclease and a guide RNA. The compositions find use in cleaving or modifying a mutHTT allele, and / or modifying the expression of a mutHTT allele. The compositions are additionally useful for treating Huntington's disease (HD), particularly in an allele-specific manner.

The present disclosure relates to nucleic acid molecules encoding Lamin A, as well as vectors and pharmaceutical compositions comprising such nucleic acid molecules for use in treatment of laminopathies.

The present invention provides a method of replacing a pathogenic amino acid using a programmable base editor system comprising a polynucleotide programmable nucleotide binding domain and a nucleobase editing domain conjugated to a guide polynucleotide. The invention also provides a base editor system for editing nucleobases of a target nucleotide sequence.

The invention relates to an antisense oligonucleotide comprising a sequence complementary to at least part of a target nucleic acid sequence, wherein the target sequence comprises SEQ ID NO: 1 or a portion thereof. The invention further relates to methods for treating, preventing ameliorating, or slowing progression of Doyne honeycomb macular dystrophy (DHMD) and related medical uses of the antisense oligonucleotides.

The present disclosure provides gRNAs for editing SERPINA1 and combinations of such gRNAs, nucleic acids encoding such gRNAs, vectors comprising such nucleic acids, RNPs comprising such gRNAs and endonucleases, pharmaceutical compositions comprising any of the foregoing, and kits comprising any of the foregoing. The present disclosure further provides methods related to such gRNAs, including methods of manufacturing, methods of effecting SERPINA1 gene editing, and methods of preventing, treating, or ameliorating a symptom of a target disease, disorder, or condition such as A1ATD.

The present invention relates to a pharmaceutical composition comprising at least five different suppressor transfer RNAs, where a) at least one of the suppressor transfer RNAs is capable of base-pairing with a UGA stop codon, at least one of the suppressor transfer RNAs is capable of base-pairing with a UAA stop codon, and at least one of the suppressor transfer RNAs is capable of base-pairing with a UAG stop codon; and b) the suppressor transfer RNAs are not all present in equal amounts in the composition, and a pharmaceutically acceptable carrier.

The invention relates to prime editing guide RNA (pegRNA) sequences, CRISPR-PE (Regularly Interrupted Palindromic Repeat Sets-Prime Editing) system and the method of transferring the aforementioned pegRNA sequences to the target region with neural lentivirus by integrating them into the CRISPR-PE system and thereby correcting the mutations for correction of pathogenic mutations, particularly the C146T / A and 778delG mutations in Retinitis Pigmentosa disease on the retinol dehydrogenase 12(RDH12) gene, for use in the treatment of Retinitis Pigmentosa (RP) disease. With the invention, PegRNA sequences that has a low indel mutation risk, high reproductive rate, and genome integration capability, and provides correction of pathogenic mutations on the RDH12 gene in Retinitis Pigmentosa, especially the C146T / A and 778delG mutations on the RDH12 gene and the CRISPR-PE system containing these sequences and the lentiviral vector for use in the treatment of Retinitis Pigmentosa with the invention are provided.

This invention provides a method for treating a disease or condition characterized by reduced expression or function of the NaV1.1 protein. [Solution] A method is provided for treating a disease or condition in a human subject or reducing the likelihood of developing it, comprising the step of administering a pharmaceutical composition comprising an antisense oligomer (ASO) to a human subject, wherein the ASO comprises a sequence having at least 80% sequence identity with respect to a specific sequence.

The present disclosure provides methods and compositions for reducing the level of an RNA transcript produced from a mutant Huntingtin (mHtt) allele in a neuron in an individual with Huntington's disease. The present disclosure provides methods for reducing the level of an RNA transcript produced from an mHTT allele in an allele-specific manner. The present disclosure provides systems and compositions for carrying out the methods.

RNA molecules comprising a guide sequence portion having 17-20 nucleotides in the sequence of 17-20 contiguous nucleotides set forth in any one of SEQ ID Nos: 1-1313 and compositions, methods, and uses thereof.

Provided are methods of treating a subject with a SCN2A-related disorder, e.g., Developmental and Epileptic Encephalopathies (DEE), comprising administering to the subject an oligomeric compound. Also provided are methods of reducing frequency of seizures experienced by a subject with a SCN2A-related disorder, comprising administering to the subject an oligomeric compound.

Described are compounds and methods useful for the treatment and investigation of diseases and disorders associated with expanded repeat-containing RNA molecules. In certain embodiments, compounds and methods useful for the modulation of ATXN-3 pre-mRNA are described. In certain embodiments, compounds and methods useful for the modulation of ATN-1 mRNA are described.

The present disclosure provides methods and compositions for generating dominant alleles using targeted editing techniques. Also provided are modified chromosomes, cells, tissues, and plants comprising modified dominant allele.

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

This disclosure provides a double-stranded RNA (dsRNA) comprising a) a first strand that hybridizes with a target CAG repeat region of CAG repeat RNA, and b) a second strand that hybridizes with the first strand, wherein the first strand comprises i) a first mismatch to the target CAG repeat region, and ii) at least a second mismatch to the target CAG repeat region. This disclosure provides recombinant nucleic acids comprising a) the dsRNA of this disclosure and b) a microRNA scaffold, and this disclosure also provides recombinant expression vectors comprising a nucleotide sequence encoding such recombinant nucleic acids. This disclosure provides viral and nonviral delivery media comprising the recombinant expression vector of this disclosure, and pharmaceutical compositions comprising such delivery media. This disclosure provides a method for selectively reducing the translation of disease-related CAG repeat-containing RNA. TIFF2026515707000003.tif130128

Among other things, the present disclosure provides various technologies including chirally controlled oligonucleotide compositions and technologies for manufacturing and using such oligonucleotide compositions. In some embodiments, the present disclosure provides technologies useful for editing of adenosine in transcripts, e.g., SERPINA1 transcripts. In some embodiments, the present disclosure provides methods for treating various conditions, disorders or diseases that can benefit from adenosine editing. In some embodiments, the present disclosure provides technologies useful for preventing or treating various conditions, disorders or diseases, e.g., alpha-1 antitrypsin deficiency.

The present disclosure provides methods and compositions for generating dominant alleles using targeted editing techniques. Also provided are modified chromosomes, cells, tissues, and plants comprising modified dominant allele.

The disclosure features methods of correcting a mutation in the human beta-globin (HBB) gene in a cell or population of cells. The disclosure also features methods of increasing repair of a DNA double stranded break (DSB) in an HBB gene by the homology-directed repair (HDR) pathway. The disclosure also features compositions for use in the methods.

Novel compositions and methods are provided that are useful for treating, preventing and potentially curing genetic diseases, such as familial Alzheimer's disease, by disrupting a genomic sequence comprising one or more SNPs that are highly epidemic in a population but independent of a particular disease, in some embodiments, their genomic positions are within the same gene exon as the disease-related alleles, and upstream of such disease-related alleles present in the genome of a treatment recipient.

SnRNA systems comprising RNA binding sequences for RNA editing are disclosed herein.

An agent for treating a common form of autosomal dominant retinitis pigmentosa (ADRP) is disclosed, wherein the agent comprises a first nucleotide sequence encoding a CRISPR-associated (Cas) endonuclease which binds to an NG or NNGRRT PAM (protospacer adjacent motif) sequence, and a second nucleotide sequence encoding or comprising a guide RNA (gRNA) capable of forming a CRISPR-Cas complex with said Cas endonuclease, wherein the gRNA is specifically targeted to a target mutant allele selected from RHOP23H and NR2E3G56R.

The present disclosure relates to double-stranded ribonucleic acid (dsRNAi) agents and compositions that target the APOE gene, and methods of using such dsRNAi agents and compositions to inhibit expression of the APOE gene and to treat subjects with APOE-associated neurodegenerative diseases or disorders, such as Alzheimer's disease and Parkinson's disease.

A method for repairing HBA2 gene mutations by single base editing and use thereof, belonging to the technical field of gene editing. The method comprises the following steps: contacting a single base editor and gRNA with an HBA gene sequence to be edited and repaired, deaminating the codon target cytosine base at CD142 in the HBA gene sequence, and converting the cytosine into thymine. According to the method, pathogenic mutation sites can be accurately edited without generating double-strand breaks and affecting chromatin conformation and genome stability, without generating random insertions of large-fragment genes into genomes, which have a low influence on cancer gene activation or tumor-inhibiting gene inactivation, and without generating random insertions / deletions at other sites of a genome. The expression of the repaired target gene is regulated by all regulatory elements of natural HBA2; therefore, the method is very safe and can also better balance the expression of α / β globin.