364results about "Polymorphism uses" patented technology

The present application provides guide RNAs and genome-editing complexes or nanoparticles that are useful for specifically targeting a mutated KRAS. Exemplary genome-editing complexes or nanoparticles comprise cell-penetrating peptides, and optionally a DNA nuclease (such as Cas9) or a polynucleotide encoding the DNA nuclease.

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.

Described herein are methods of inhibiting an allele that contains a mutation in a cell (e.g., treating a subject with an allele that contains a mutation). The method includes delivering to the cell an antisense oligonucleotide that targets a variant allele that is in cis with the mutation (e.g., the mutation is a gain of function mutation or a dominant negative mutation), wherein the cell or subject is heterozygous for the target variant, and the antisense molecule is effective at knocking down expression the target variant allele (e.g., effective at preventing, treating, or ameliorating at least one symptom associated with the mutation). Also described herein are methods of haplotyping a cell or subject, and antisense oligonucleotides that target mutant superoxide dismutase 1 (SOD1) and other genes.

Provided herein are methods and compositions for genetically engineering a cell (e.g., a hematopoietic cell) using CRISPR / Cas systems and homology-directed repair, genetically engineered cells produced by such methods, and methods involving administering such genetically engineered cells to a subject, such as a subject having a genetic disease.

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.

The invention relates to an adeno-associated virus vector for treating yolk-like macular degeneration. Aspects of the present disclosure relate to methods and compositions useful for the treatment of yolk-like macular dystrophy, such as yolk-like macular degeneration.

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.

To provide an antisense oligonucleotide for preventing, delaying, and / or treating a human cis-element repeat instability-associated genetic disorder.SOLUTION: A medicament comprises, as an active ingredient, an oligonucleotide, wherein the oligonucleotide comprises 2'-O-methyl RNA nucleotide residues, has a backbone with at least one phosphate moiety being replaced by a phosphorothioate moiety, and comprises or consists of a repetitive nucleotide unit (XYG)m, wherein m is an integer from 4 to 12, each X is C or 5-methylcytosine, each Y is U or 5-methyluracil, and at least one X is 5-methylcytosine.SELECTED DRAWING: None

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.

The invention relates to the field of diseases caused by alcohol intolerance, for example, diseases caused by ALDH2 * 2 mutation in the human ALDH2 gene. The present invention relates to oligonucleotides and their use in RNA editing methods for targeting a target adenosine in an endogenous human ALDH2 transcript in a cell, for example, Ggt in a mutant ALDH2 gene transcription molecule encoding a mutant p.E504K ALDH2 protein; a mutation, especially in the liver.

The present disclosure provides methods for treating autosomal dominant diseases in a subject. In some aspects, the methods involve the use of a gene editing enzyme with a pair of unique guide RNA sequences that targets both mutant and wildtype forms of autosomal dominant disease-related gene for destruction in cells, and then supplying the cells with wildtype autosomal dominant disease-related gene cDNA which is codon modified to evade recognition by the guide RNAs. These methods are broadly applicable to any autosomal dominant disease.

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

The present disclosure describes gene editing systems and therapeutics for use in treating VEXAS syndrome. In particular, the disclosure describes lipid nanoparticles that enhance the targeted delivery of gene editing systems and therapeutics to blood cell progenitor cells, enabling treatment of VEXAS syndrome, in vivo or ex vivo.

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.

To provide a C9orf72 oligonucleotide, a composition, and a method for treatment of C9orf72-associated conditions, disorders, or diseases including amyotrophic lateral sclerosis and frontotemporal dementia.SOLUTION: Provided is an oligonucleotide comprising at least one modification of a sugar, a base, or an internucleotidic linkage, wherein the base sequence of the oligonucleotide is or comprises at least 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 contiguous bases of a base sequence that is at least 80% identical with or complementary to a base sequence of a C9orf72 gene or a transcript thereof, and wherein a nucleobase at a 3' end of the oligonucleotide is optionally replaced by a replacement nucleobase selected from I, A, T, U, G, and C.SELECTED DRAWING: None

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.

The present disclosure provides double-stranded oligonucleotides, compositions and methods related thereto.The present disclosure encompasses the recognition that the structural elements of double-stranded oligonucleotides, such as base sequence, chemical modifications (e.g., sugar, base and / or internucleotide bond modifications) or patterns thereof, and / or stereochemistry (e.g., backbone chiral center (chiral internucleotide bond) stereochemistry) and / or patterns thereof, can have significant effects on the properties and activities of oligonucleotides, such as RNA interference (RNAi) activity, stability, delivery, etc.The present disclosure also provides methods of treating diseases using the provided double-stranded oligonucleotide compositions, for example, in RNA interference.

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