243results about "Polymorphism uses" patented technology

The present disclosure, in some aspects, relates to antisense oligonucleotides (ASO) for use in the prevention or treatment of a disease or a condition associated with low- density lipoprotein (LDL) in a subject. In some embodiments, the ASO effects site-directed adenosine-to-inosine (A-to-l) editing of a target adenosine in a target RNA sequence derived from a sequence of an endogenous low-density lipoprotein receptor (LDLR) gene such that: a) the modified LDLR protein has: (i) reduced binding to the inducible degrader of the LDLR protein (IDOL); (ii) increased stability; (iii) improved resistance to IDOL-mediated degradation; (iv) increased LDLR protein expression; and / or (v) increased activity or function to take up LDL; and / or b) editing of the 3'-untranslated region (UTR) of the target RNA leads to an increase in LDLR protein expression and / or stability.

The disclosure features systems and methods for 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.

Among other things, the present disclosure provides designed oligonucleotides and compositions thereof. In some embodiments, oligonucleotides and compositions of the present disclosure can provide high levels of adenosine editing. In some embodiments, oligonucleotides and compositions of the present disclosure are useful for treating various conditions, disorders or diseases, e.g., alpha-1 antitrypsin deficiency. In some embodiments, the present disclosure provides methods for treating various conditions, disorders or diseases that can benefit from adenosine editing.

Disclosed herein are polynucleic acid molecules, pharmaceutical compositions, and methods of use for PRKAG2 antibody oligonucleotide conjugates (AOC).

Among other tilings, 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 allele-specific knockdown of mutant Huntingtin transcripts. In some embodiments, the present disclosure provides technologies usefill for reducing the expression, level, amount, and / or activity of mutant Huntingtin transcripts or products thereof. In some embodiments, the present disclosure provides methods for treating Huntington's disease.

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 application relates to the field of medicine, in particular to oligonucleotide, viral vector and its application and RNAi drug preparation. The oligonucleotide is one or two of the nucleic acid sequences shown in SEQ ID NO: 1 to SEQ ID NO: 7; or the oligonucleotide with the nucleic acid sequence of the above-mentioned oligonucleotide is not less than 80% consistent. The present application finds that the RNAi drug can significantly reduce the expression of mutant COL8A2, can treat the corneal dystrophy that has occurred, and can prevent the occurrence of corneal dystrophy. It can be seen that the RNAi drug preparation of the present application can effectively treat and prevent the corneal dystrophy caused by COL8A2 mutation.

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.

The present invention relates to compositions and methods for subpopulation-specific modulation of cell function and for treating repeat expansion disorders comprising genetic, degenerative, neurological and cellular diseases, including immune disorders. Also provided are research kits for subpopulation-specific modulation of protein activity and the corresponding potential to discover novel therapeutic compositions. More specifically, the disclosed compositions and methods selectively up- or downregulate at least a first population of a cellular protein or therapeutic target with minimal or negligible effect on the activity of at least a second population of the cellular protein or therapeutic target.

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

Phospholamban (PLN) is a critical regulator of calcium cyclin and contractility in the heart. The deletion of Arginine 14 of the phospholamban gene (R14del) is associated with the pathogenesis of an inherited form of cardiomyopathy with prominent arrhythmias. Although the genetic etiology is well defined, there are currently no therapies for this rare disease. This disclosure provides an allele-specific silencing approach by interfering RNA (RNAi) to reduce the expression levels of the R14del allele of the PLN gene.

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 invention relates to editing oligonucleotides (EONs) that carry stereospecific phosphorothioate internucleotide linkage modifications at specified positions and that do not carry such modifications on positions that would lower RNA editing efficiency. The selection of positions that should or should not carry a phosphorothioate Rp and / or Sp configuration modification is based on computational modelling that revealed incompatibilities of the stereospecific linkages with the intermolecular oxygen-mediated hydrogen bond network.

Disclosed herein are SnRNA systems containing RNA-binding sequences for RNA editing.

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.

The present invention relates to the field of diseases caused by high levels of LDL-C and / or fibrinogen, such as cardiovascular diseases. The present invention includes an oligonucleotide for RNA editing technology that deaminates a target adenosine nucleotide, such as adenosine at position 1055, in the transcript of the human B4GALT1 gene.

Among other things, the present disclosure provides designed oligonucleotides and compositions thereof. In some embodiments, oligonucleotides and compositions of the present disclosure can provide high levels of adenosine editing. In some embodiments, oligonucleotides and compositions of the present disclosure are useful for treating various conditions, disorders or diseases, e.g., alpha- 1 antitrypsin deficiency. In some embodiments, the present disclosure provides methods for treating various conditions, disorders or diseases that can benefit from adenosine editing.

To provide methods of using base editors comprising adenosine deaminase variants for altering mutations associated with Glycogen Storage Disease Type 1a (GSD1a).SOLUTION: The present invention provides a method of editing a glucose-6-phosphatase (G6PC) polynucleotide comprising a single nucleotide polymorphism (SNP) associated with Glycogen Storage Disease Type 1a (GSD1a). The method comprises contacting the G6PC polynucleotide with an adenosine deaminase base editor 8 (ABE8) in a complex with one or more guide polynucleotides, wherein the adenosine deaminase base editor 8 (ABE8) comprises a polynucleotide programmable DNA binding domain and an adenosine deaminase domain, and wherein the one or more of guide polynucleotides target the base editor to effect an A T to G C alteration of the SNP associated with the GSD1a.SELECTED DRAWING: None

The present invention relates to methods and compositions for disrupting interaction of an NRF2 protein and a KEAP1 protein. The methods include contacting at least one polynucleotide selected from the group consisting of a polynucleotide encoding the NRF2 protein and a polynucleotide encoding the KEAP1 protein with a guide oligonucleotide that effects one or more (e.g., at least two) adenosine deaminase acting on RNA (ADAR)-mediated adenosine to inosine alterations in said at least one polynucleotide, wherein the adenosine to inosine alterations generate a mutant amino acid, thereby disrupting interaction of the NRF2 protein and the KEAP1 protein. The invention also relates to methods of treating a KEAP1-NRF2 pathway related disease in a subject in need thereof, the method comprising contacting, within the subject, at least one polynucleotide selected from the group consisting of a polynucleotide encoding an NRF2 protein and a polynucleotide encoding a KEAP1 protein with a guide oligonucleotide that effects an adenosine deaminase acting on RNA (ADAR)-mediated adenosine to inosine alteration in said at least one polynucleotide, wherein the adenosine to inosine alteration generates a mutant amino acid, thereby disrupting interaction of the NRF2 protein and the KEAP1 protein and treating the disease in the subject; and compositions thereof.

Described herein are compounds, compositions, and methods for modulating KRAS expression, such as mutated KRAS expression, and / or downstream signaling pathways. Also described herein are compounds, compositions, and methods for treating a disease or condition associated with mutated KRAS. In some embodiments, the compound comprises at least one antisense oligonucleotide that, upon being delivered into a cell, hybridizes to an endogenous KRAS mRNA, which leads to the degradation of the KRAS mRNA. In some embodiments, the antisense oligonucleotide hybridizes to an mRNA encoding a mutated KRAS protein, such as a KRAS protein comprising a G12C mutation, a G12V mutation, a G12D mutation, or a G12A mutation.

Methods and compositions for modifying the coding sequence of endogenous genes using rare-cutting endonucleases and transposases. The methods and compositions described herein can be used to modify the coding sequence of endogenous genes.

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.

To provide oligonucleotides, compositions and methods.SOLUTION: Among other things, the present disclosure provides oligonucleotides, compositions, and methods for preventing and / or treating various conditions, disorders or diseases. In some embodiments, provided oligonucleotides comprise nucleobase modifications, sugar modifications, internucleotidic linkage modifications and / or patterns thereof, and have improved properties, activities and / or selectivities. In some embodiments, the present disclosure provides oligonucleotides, compositions and methods for HTT-related conditions, disorders or diseases, such as Huntington's disease.SELECTED DRAWING: Figure 1A

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.

To provide HSD17B13 variants and uses thereof.SOLUTION: Provided herein is an HSD17B13 variant discovered to be associated with: reduced alanine and aspartate transaminase levels; a reduced risk of chronic liver diseases; and reduced progression from simple steatosis to more clinically advanced stages of chronic liver disease. Also provided herein are isolated nucleic acids and proteins related to variants of HSD17B13, and cells comprising those nucleic acids and proteins. Also disclosed is a method for modifying a cell via the use of any combination of: a nuclease agent to express a recombinant HSD17B13 gene or a nucleic acid encoding an HSD17B13 protein; an exogenous donor sequence; a transcription activator; a transcription repressor; and an expression vector. Also disclosed is a therapeutic and prophylactic method for treating a subject having or at risk of developing chronic liver disease.SELECTED DRAWING: Figure 17

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.