The disclosure relates to double stranded ribonucleic acid (dsRNAi) agents and compositions targeting an APOE gene, as well as methods of inhibiting expression of an APOE gene and methods of treating subjects having an APOE-associated neurodegenerative disease or disorder, e.g., Alzheimer's disease and Parkinson's disease, using such dsRNAi agents and compositions.

The invention provides siRNA compositions that specifically downregulates expression of a variant of the PNPLA3 gene and methods of use thereof for treating a chronic liver disease or alcoholic liver disease (ALD).

Described herein are compositions for targeting and editing genomes. Also described herein are methods for targeting and editing genomes utilizing the compositions in the instant disclosure.

The invention provides for a method for selectively reducing the expression of a mutant mRNA and/or protein having an expanded nucleotide repeat relative to a wild-type mRNA, comprising contacting a cell with an antisense oligonucleotide of sufficient length and complementarity to the expanded nucleotide repeat. More particularly it relates to selectively reducing the expression of mutant Huntington protein associated with Huntington's disease. The antisense oligonucleotide comprising either a nucleotide or a repeated three nucleotide sequence as defined in the claims.

In some aspects, the disclosure relates to compositions and methods for treating fibrodysplasia ossificans progressiva (FOP) in a subject. In some aspects, the disclosure provides isolated nucleic acids, and vectors such as rAAV vectors, configured to express transgenes that inhibit (e.g., decrease) expression of mutated AVCR1 gene in muscle cells or connective tissues.

Provided herein are antisense oligonucleotides and prophylactic and therapeutic methods featuring such oligonucleotides. These oligonucleotides and methods are useful for treating or preventing ataxia telangiectasia in a subject. Specifically, the disclosure provides antisense nucleobase oligomers each comprising (8-40) nucleobases, wherein at least 90% of said nucleobases or more than (8) consecutive nucleobases of the oligomer are complementary to a nucleic acid sequence in an Ataxia-Telangiectasia Mutated (ATM) allele comprising a mutation associated with aberrant splicing.

Disclosed herein are engineered guide RNAs, engineered polynucleotides, precursor engineered polynucleotide, vectors omprising engineered polynucleotide, nucleic acids of engineered polynucleotide, pharmaceutical compositions thereof, methods of making the engineered polynucleotides and methods of treating or preventing a disease or condition by administering above described thereof.

The present disclosure relates to compounds useful for the detection or modulation of target nucleic acids, including DNA and RNA. The present disclosure further relates to methods for treatment of trinucleotide repeat disorders, which can include administration of oligonucleotide analogues that can bind pathogenic nucleotide repeats in DNA or RNA.

Provided herein are compositions and methods relating to providing or engineering a structural target to attract ADAT editing to a desired site. Further provided herein are compositions and methods relating to recombinant adenosine deaminase acting on tRNA (ADAT) guide tRNAs (adat-gtRNA). In certain embodiments, such compositions and methods will be useful for modifying a coding sequence of a desired protein. Also provided are methods of treating a disease or disorder associated with loss of wild-type protein expression.

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.