Abstract: The disclosure relates to use of double stranded ribonucleic acid (dsRNAi) agents and compositions targeting an amyloid precursor protein (APP) gene, including methods of inhibiting expression of an APP gene and methods of treating subjects having a disease or disorder characterized by enlarged endosomes, e.g., Alzheimer's disease (AD) and Down syndrome (DS), particularly occurrences of such neurodegenerative diseases associated with one or more mutations in presenilin 1 (PSEN1), using such dsRNAi agents and compositions.

Abstract: The present invention relates to RNAi agents, e.g., double stranded RNA (dsRNA) agents, targeting the KISS1 gene. The invention also relates to methods of using such RNAi agents to inhibit expression of a KISS1 gene and to methods of preventing and treating a deficiency in glycemic control, e.g., type 2 diabetes mellitus (T2DM).

Abstract: One aspect of the present invention relates to double-stranded RNA (dsRNA) agent capable of inhibiting the expression of a target gene. 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.

Abstract: The present disclosure relates to double stranded RNA agents targeting the hepatitis B virus (HBV) genome, and methods of using such agents to inhibit expression of one or more HBV genes and methods of treating subjects having an HBV infection or HBV-associated disorder, e.g., chronic hepatitis B infection.

Abstract: The present invention relates to ligand conjugates of oligonucleotides (e.g., iRNA agents) and methods for their preparation. The ligands are derived primarily from monosaccharides These conjugates are useful for the in vivo delivery of oligonucleotides.

Abstract: One aspect of the present invention relates to double-stranded RNA (dsRNA) agent capable of inhibiting the expression of a target gene. The sense strand of the dsRNA agent comprises at least one thermally destabilizing nucleotide, and at least one said thermally destabilizing nucleotide occurring at a site opposite to the seed region (positions 2-8) of the antisense strand; and the antisense strand of the dsRNA agent comprises at least two modified nucleotides that provide the nucleotide a steric bulk that is less than or equal to the steric bulk of a 2?-OMe modification, wherein said modified nucleotides are separated by 11 nucleotides in length. Other aspects of the invention relates to pharmaceutical compositions comprising these dsRNA agents suitable for therapeutic use, and methods of inhibiting the expression of a target gene by administering these dsRNA agents, e.g., for the treatment of various disease conditions.

Abstract: The disclosure relates to RNA agents modified for targeted delivery to the eye. The present invention provides modified double stranded ribonucleic acid (dsRNAi) agents conjugated to an integrin targeting ligand, as well as methods of modulating the expression of a target gene in an ocular cell or tissue and methods of treating subjects having an ocular disease or disorder using such dsRNAi agents.

Abstract: The disclosure relates to double-stranded ribonucleic acid (dsRNA) compositions targeting ANGPTL7. The invention also relates to methods of using such dsRNA compositions to inhibit expression of ANGPTL7 and to methods of treating ANGPTL7-associated disorders, e.g., glaucoma, using such dsRNA compositions.

Abstract: The invention relates to a double-stranded ribonucleic acid (dsRNA) targeting a mutant Epidermal Growth Factor Receptor (EGFR), and methods of using the dsRNA to inhibit expression of mutant EGFR.

Abstract: The invention relates to a double-stranded ribonucleic acid (dsRNA) targeting a Serum Amyloid A (SAA) gene, and methods of using the dsRNA to inhibit expression of SAA.

Abstract: The disclosure relates to double-stranded ribonucleic acid (dsRNA) compositions targeting MYOC, and methods of using such dsRNA compositions to alter (e.g., inhibit) expression of MYOC.

Abstract: The present invention relates to RNAi agents, e.g., double stranded RNAi agents, targeting a xanthine dehydrogenase (XDH) gene, and methods of using such double stranded RNAi agents to inhibit expression of an XDH gene and methods of treating subjects having an XDH-associated disease.

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

Abstract: The disclosure relates to double stranded ribonucleic acid (dsRNAi) agents and compositions targeting a leucine-rich repeat kinase 2 (LRRK2) gene, as well as methods of inhibiting expression of a LRRK2 gene and methods of treating subjects having a LRRK2-associated disease or disorder, e.g., Parkinson's disease, using such dsRNAi agents and compositions.

Abstract: The disclosure relates to double stranded ribonucleic acid (dsRNAi) agents and compositions targeting an ATXN2 gene, as well as methods of inhibiting expression of an ATXN2 gene and methods of treating subjects having an ATXN2-associated neurodegenerative disease or disorder, e.g., SCAs and ALS, using such dsRNAi agents and compositions.

Abstract: The invention relates to RNAi agents, e.g., double-stranded RNAi agents, targeting the Serpina1 gene, and methods of using such RNAi agents to inhibit expression of Serpina1 and methods of treating subjects having a Serpina1 associated disease, such as a liver disorder.

Abstract: The invention relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the FLCN gene, as well as methods of inhibiting expression of FLCN, and methods of treating subjects that would benefit from reduction in expression of FLCN, such as subjects having a FLCN-associated disease, disorder, or condition, using such dsRNA compositions.

Abstract: The present invention provides a phosphorothioate-modified oligonucleotide comprising a structure shown below: The present invention also provides a phosphorothioate-modified oligonucleotide comprising a structure having formula (CIII):

Abstract: The disclosure relates to double stranded ribonucleic acid interference (dsRNAi) agents and compositions targeting a microtubule-associated protein tau (MAPT) gene, as well as methods of inhibiting expression of a MAPT gene and methods of treating subjects having a MAPT-associated disease or disorder, e.g., Alzheimer's disease, frontotemporal dementia, progressive supranuclear palsy, or other tauopathies, using such dsRNAi agents and compositions.

Abstract: Carbonic anhydrase inhibitors have been shown to reduce aqueous humor production and thereby reduce intraocular pressure in the eye. Accordingly, there is a need for agents that can selectively and efficiently inhibit expression of the CA2 gene such that subjects having a CA2-associated disorder, such as glaucoma, can be effectively treated. The disclosure relates to double-stranded ribonucleic acid (dsRNA) compositions targeting carbonic anhydrase 2 (CA2), and methods of using such dsRNA compositions to alter (e.g., inhibit) expression of carbonic anhydrase 2.