The present invention relates to methods and compositions for editing an ASS1 polynucleotide, e.g., an ASS1 polynucleotide comprising a SNP associated with Citrullinemia Type 1. The invention also relates to methods and compositions for treating or preventing Citrullinemia Type 1 in a subject.

One aspect of the present invention relates to a small circular interfering RNA (sciRNA) comprising a sense strand and an antisense strand, each of said sense and antisense strands comprising at least one nucleic acid modification, optionally wherein the sense strand has a circular or substantially circular structure. Other aspects of the invention relate a pharmaceutical composition and a method for inhibiting the expression of a target gene in a subject using the sciRNA.

The present disclosure provides CRISPR/Cas9 ribonucleoprotein compositions comprising chemically modified CRISPR RNA (crRNA) guide and trans-acting CRISPR RNA (tracrRNA) components. Methods of using the disclosed CRISPR/Cas9 ribonucleoprotein compositions are also provided.

The present invention relates to RNAi constructs for reducing expression of the PNPLA3 gene. Methods of using such RNAi constructs to treat or prevent liver disease, nonalcoholic fatty liver disease (NAFLD) are also described.

Provided are aptamers and aptamer compositions and particularly, although not exclusively, to a bi-specific aptamer capable of binding a tumor cell antigen and an immune cell surface protein.

One aspect of the present invention relates to double-stranded RNA (dsRNA) agent capable of inhibiting the expression of a target gene. The antisense strand of the dsRNA molecule comprises at least one thermally destabilizing nucleotide occurring at a seed region; the dsRNA comprises at least four 2′-fluoro modifications, and the sense strand of the dsRNA molecule comprises ligand, wherein the ligand is an ASGPR ligand. Other aspects of the invention relate to pharmaceutical compositions comprising these dsRNA molecules suitable for therapeutic use, and methods of inhibiting the expression of a target gene by administering these dsRNA molecules, e.g., for the treatment of various disease conditions.

The invention relates to double stranded ribonucleic acid (dsRNAi) agents and compositions targeting the SCAP gene, as well as methods of inhibiting expression of a SCAP gene and methods of treating subjects having a SCAP-associated disorder, such as nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH), using such dsRNAi agents and compositions.

The present invention concerns methods and reagents useful in modulating gene expression in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. Specifically, the invention relates to synthetic chemically modified small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin NA (shRNA) molecules capable of mediating RNA interference (RNAi) against target nucleic acid sequences. The small nucleic acid molecules are useful in the treatment of any disease or condition that responds to modulation of gene expression or activity in a cell, tissue, or organism.

The present disclosure relates generally to cleavable linkers and uses thereof.

Provided are aptamers and aptamer compositions and particularly, although not exclusively, to a bi-specific aptamer capable of binding a tumor cell antigen and an immune cell surface protein.