502results about "Polymorphism uses" patented technology

The disclosure is directed to methods for treating a cancer in a subject in need thereof by administering to the subject a bifunctional short hairpin (shRNA) molecule capable of inhibiting the expression of at least one mutated KRAS gene and at least one KRAS inhibitor.

Among other things, the present disclosure provides oligonucleotides, compositions, and methods thereof. Among other things, the present disclosure encompasses the recognition that structural elements of oligonucleotides, such as base sequence, chemical modifications (e.g., modifications of sugar, base, and / or internucleotidic linkages) or patterns thereof, conjugation with additional chemical moieties, and / or stereochemistry [e.g., stereochemistry of backbone chiral centers (chiral internucleotidic linkages)], and / or patterns thereof, can have significant impact on oligonucleotide properties and activities, e.g., knockdown ability, stability, delivery, etc. In some embodiments, the oligonucleotides decrease the expression, activity and / or level of a C9orf72 gene, including but not limited to, one comprising a repeat expansion, or a gene product thereof. In some embodiments, the present disclosure provides methods for treatment of diseases using provided oligonucleotide compositions, for example, in treatment of C9orf72-related disorders.

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 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.

Compositions and methods are provided for the treatment or prophylaxis of amyloid pathologies such as Alzheimer's Disease.

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 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.

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.

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 SNORD1091B. The present invention further relates to pharmaceutical compositions and methods for treatment of Angelman syndrome.

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.

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

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.

Disclosed herein are modulators of a long non-coding RNA (IncRNA), wherein an expression of the IncRNA is associated with idiopathic pulmonary fibrosis. Further provided herein are methods of treating idiopathic pulmonary fibrosis a subject in need thereof. Also, provided herein are methods of predicting severity and progression of idiopathic pulmonary fibrosis based on expression of the IncRNAs described herein.

Streptococcus pyogenes Cas9 (SpCas9) variants with relaxed PAM requirements capable of high-resolution editing for various applications, and methods of use thereof.

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

Provided herein are compositions and methods of using base editors comprising a polynucleotide programmable nucleotide binding domain and a nucleobase editing domain in conjunction with a guide polynucleotide. Also provided herein are base editor systems for editing nucleobases of target nucleotide sequences.

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.

To provide a metabolically stable phosphorothioate-modified RNA.SOLUTION: The present invention provides a modified oligonucleotide, having a 5' end and a 3' end, and comprising a sense strand and an antisense strand complementary to a target, and at least one modified intersubunit linkage of Formula I, where at least one modified oligonucleotide is incorporated into the antisense strand or sense strand of an siRNA.SELECTED DRAWING: None

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 provides compositions comprising novel adenosine base editors (e.g., ABE8) with increased efficiency, and methods of using base editors comprising adenosine deaminase variants to alter mutations associated with glycogen storage disease type 1a (GSD1a).

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.

In general, the current disclosure relates to the tRNAs that encode for one amino acid but are covalently linked to a different amino acid. The tRNAs can correct missense mutations by providing a different amino acid during protein synthesis. Such tRNAs can be used to correct disease-causing missense mutations.