The invention relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the ALAS1 gene, and methods of using such dsRNA compositions to alter (e.g., inhibit) expression of ALAS1.

This application relates to therapeutic siRNA agents and methods of making and using the agents.

The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of gene expression and/or activity, and/or modulate a gene expression pathway. Specifically, the invention relates to double-stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA) molecules that are capable of mediating or that mediate RNA interference (RNAi) against target gene expression.

Provided herein, in some embodiments, are materials and methods for treating hemophilia A in a subject ex vivo or in vivo. Also provided herein, in some embodiments, are materials and methods for knocking in a coding sequence encoding a synthetic FVIII having a B domain substitute into a genome.

Described are RNAi agents, compositions that include RNAi agents, and methods for inhibition of a Receptor for Advanced Glycation End-products (AGER or RAGE) gene. The RAGE RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of an AGER gene. Pharmaceutical compositions that include one or more RAGE RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described RAGE RNAi agents to pulmonary cells, in vivo, provides for inhibition of AGER gene expression and a reduction in membrane RAGE activity, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including pulmonary inflammation diseases such as severe asthma.

The present invention provides oligonucleotides comprising 2′-O-methyl (2′-OMe) and 2′-deoxy-2′-fluoro (2′-F) modifications, compositions thereof, and methods of use for reducing the expression or activity of a gene.

siRNA compositions are provided that contain gemcitabine (GEM) in place of cytosine moieties within the siRNA sequence. Pharmaceuticals compositions containing these siRNA molecules, and methods of using the compositions for treating diseases such as cancer are provided.

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.

A novel anti-tumor agent capable of delivering siRNA or shRNA specifically to pancreatic cancer cells and suppressing tumor growth, invasion, and metastasis of pancreatic cancer is provided. The present invention provides a nucleic acid delivery enhancer for delivering siRNA or shRNA into cells, which consists of a folic acid-cationic oligopeptide complex. The present invention also provides an anti-tumor agent having siRNA or shRNA capable of binding to mRNA or snoRNA expressed in pancreatic cancer cells to inhibit its expression and a folic acid-cationic oligopeptide complex. The siRNA is capable of binding to RNA selected from the group consisting of, for example, SNORA18 snoRNA, NUP85 mRNA, WASF2 mRNA, and SNORA22 snoRNA.

Provided herein are methods for the treatment of polycystic kidney disease, including autosomal dominant polycystic kidney disease, using modified oligonucleotides targeted to miR-17.