30results 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 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.

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 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.

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 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.

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

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.

Provided are methods for editing RNA by introducing a deaminase-recruiting RNA in a host cell for deamination of an adenosine in a target RNA, deaminase-recruiting RNAs used in the RNA editing methods, compositions and kits comprising the same.

Methods of preventing or treating liver disease in a subject characterised as having a PNPLA3- 148M protein variant are provided. The methods include administering to the subject an oligonucleotide or a DNA molecule encoding an oligonucleotide, wherein the oligonucleotide is capable of effecting ADAR-mediated editing of a polynucleotide encoding the PNPLA3-148M protein variant, and wherein the polynucleotide encoding the PNPLA3-148M protein variant undergoes ADAR-mediated editing at a codon encoding the methionine at position 148 such that the polynucleotide encodes a PNPLA3-148V protein variant. The disclosure also provides methods of editing a target ribonucleic acid (RNA) molecule encoding a PNPLA3-148M protein variant and methods of restoring the function of the PNPLA3 protein in a subject characterised as having the PNPLA3-148M protein variant.

This disclosure provides, for example, compositions, systems, and methods for targeting, editing, modifying, or manipulating the host cell genome at one or more locations within a DNA sequence in a cell, tissue, or subject. An improved gRNA scaffold compatible with St1Cas9 is described.

Compositions and methods for cleaving mutant huntingtin (mutHTT) alleles are provided. The compositions comprise CRISPR RNA, a guide RNA, and an encoding nucleic acid molecule. Vectors and host cells comprising the nucleic acid molecule are also provided. Further provided are RNA-induced nuclease (RGN) systems for cleaving mutHTT alleles, wherein the RGN system comprises an RNA-induced nuclease and a guide RNA. The compositions are useful for cleaving or modifying mutHTT alleles and / or modifying the expression of mutHTT alleles. The compositions are even more useful for the treatment of Huntington's disease (HD), particularly in an allele-specific manner.

Described herein are compositions and methods for highly efficient and specific base-editing to correct two distinct X-linked chronic granulomatous disease (X-CGD) mutations, CYBB c.676C>T and c.1075G>A.

Described herein is the preferential knockdown of the mutant transcript ACVR1R206H and inhibition of osteogenic differentiation using allele-selective gapmers for the treatment of Fibrodysplasia Ossificans Progressiva.

The invention relates to the field of human genetics, more specifically to treatments for a disease or condition associated with an abnormal processing of the Amyloid Precursor Protein (APP), preferably familiar Alzheimer disease (FAD). The invention in particular relates to antisense oligonucleotides (AON's) that can be used for treating such diseases or conditions.

This invention provides a method for knocking out the expression of a dominant mutant allele by disrupting the dominant mutant allele or by degrading the resulting mRNA. [Solution] A method for inactivating a mutant allele of the neutrophil elastase gene (ELANE gene) having a mutation related to severe congenital neutropenia (SCN) or cyclic neutropenia (CyN) in a cell, wherein the cell is a specific heterozygote expressing an allele having a mutation encoding a disease-causing mutant protein, and the method comprises introducing into the cell a composition comprising a CRISPR nuclease or a sequence encoding the CRISPR nuclease and a first RNA molecule comprising a guide sequence of 21 to 30 nucleotides, wherein the complex of the CRISPR nuclease and the first RNA molecule acts to break the double-strand of the mutant allele of the ELANE gene.

Disclosed herein are systems for repairing or causing mutational correction to a mutant allele and uses thereof for treatment of genetic disorders.

The present disclosure provides for systems, methods, and compositions for targeting and editing nucleic acids. In particular, the present disclosure provides non-naturally occurring or engineered RNA-targeting systems comprising a RNA-targeting Cas13 protein, at least one guide molecule, and at least one adenosine deaminase protein or catalytic domain thereof.

The present invention provides iRNA agents, e.g., double stranded iRNA agents, that target the transthyretin (TTR) gene and methods of using such iRNA agents for treating or preventing TTR-associated ocular diseases.

The present invention relates to the treatment of Pyruvate Kinase Deficiency (PKD) using the Clustered-Regularly Interspaced Short Palindromic Repeats (CRISPR) system. This technology offers the possibility to design an improved single guide RNA (sgRNA), in particular, an improved crRNA to be associated with tracrRNA, which is incorporated into a CRISPR-associated protein (Cas9) to recognize and induce DNA double-strand breaks at a specific target location. DNA double-strand breaks will be repaired by homologous recombination (HR) in the presence of a donor sequence for PKLR gene repair.

The present disclosure provides methods of editing RHO using a prime editor (e.g., for correcting a P23H mutation in a RHO protein) and a pegRNA. Such methods may be useful for treating or preventing retinitis pigmentosa. The present disclosure also provides pegRNAs, ngRNAs, complexes, systems, and compositions for editing RHO and treating or preventing retinitis pigmentosa. Polynucleotides, vectors, cells, and kits for editing RHO and treating or preventing retinitis pigmentosa are also provided herein.

The disclosure provides methods, base editors, vectors encoding base editors and cognate gRNAs, and compositions and kits comprise said components, for installing nucleobase edits to the SMN2 locus to increase the activity and / or amount and / or stability of SMN2 protein in a cell, thereby treating Spinal Muscular Atrophy. In certain aspect, the disclosure provides compositions and methods to edit C840T of exon 7 of the SMN2 gene, or installing another one or more nucleobase edits which have the effect of removing or inactivating a degron, such as the C-terminal portion of the region encoded by exon 6 or the 4-amino acid region encoded by exon 8 (i.e., the EMLA (SEQ ID NO: 466) -tail) so as to remove or limit their degron activity to reduce, mitigate, or eliminate the intracellular degradation of the SMN2 protein.

This invention provides a nucleic acid trans-splicing molecule that can correct mutations in the ABCA4 gene or the CEP290 gene. [Solution] A nucleic acid trans-splicing molecule comprising (a) a binding domain configured to bind to a target ABCA4 intron selected from the group consisting of introns 19, 23, or 24, functionally linked in either the 3' to 5' direction or the 5' to 3' direction; (b) a splicing domain configured to mediate trans-splicing; and (c) a coding domain containing a functional ABCA4 exon. A composition comprising the nucleic acid trans-splicing molecule may be useful in treating or preventing diseases associated with mutations within ABCA4, such as Stargardt disease (e.g., Stargardt disease type 1), or diseases associated with mutations in CEP290, such as LCA (e.g., LCA10).

The present invention relates to oligonucleotides that are capable of inducing expression of ubiquitin-protein ligase E3A (UBE3A) from the paternal allele in animal or human neurons. The oligonucleotides target the suppressor of the UBE3A paternal allele by hybridization to SNHG14 long non-coding RNA downstream of SNORD109B. The present invention further relates to pharmaceutical compositions and methods for treatment of Angelman syndrome.

A method of treating a retinal disease in a subject in need thereof, the method comprising administering to the subject a vector that comprises a mirtron for knocking down expression of a target gene expressed in the retina and a gene therapy vector comprising a mirtron for rhodopsin knock-down.