Described herein are antiviral silencing RNA molecules (siRNAs), pharmaceutical compositions comprising same and uses thereof for the treatment of viral infections. In embodiments the siRNAs comprises chemically modification(s) for enhanced cell penetrating abilities and/or for greater nuclease resistance. Examples of chemical modifications include substituting one or more nucleotides of a native siRNA molecule with 2′-O-Methylnucleoside, 2′-Fluoronucleoside, aminoalkyl-nucleotide, aminoethyl-nucleotide, and/or 5′-aminopropyl-2′-OMe-nucleoside. The chemically modified nucleotides may be incorporated into the P strand, the G strand or both. Other possible modifications include coupling a compound such as a spermine molecule to the 5′ terminus or the 3′ terminus of the siRNA.

The present invention is directed to hybrid chimera antisense oligonucleotides including deoxyribonucleotide and 2′-deoxy-2′-fluoro-β-D-arabinonucleotide which binds to a Foxp3 mRNA, and to methods of use thereof. The methods include the use for reducing expression level of Foxp3 gene, increasing anti-tumor activity, and treating cancer in a subject.

The present invention relates to RNAi agents, e.g., double stranded RNA (dsRNA) agents, targeting the G protein-coupled receptor 146 (GPR146). The invention also relates to methods of using such RNAi agents to inhibit expression of a GPR146 gene and to methods of preventing and treating a GPR146-associated disorders, e.g., hypercholesterolemia and atherosclerosis.

Disclosed are methods and compositions related to unique combinations of 2 or more RNA sequences including but not limited to microRNA, mRNA, long non-coding RNA, y-RNA, pi-RNA and other non-coding RNA packaged within naturally produced mesenchymal stem/stromal cell extracellular vesicles (EVs), synthetic EVs (aka liposomes or lipid nanoparticles), or in combination thereof that are capable of modifying immune function in a subject.

Compositions and methods for editing, e.g., introducing double-stranded breaks, within the KLKB1 gene are provided. Compositions and methods for treating subjects having hereditary angioedema (HAE), are provided.

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.

The present invention relates to antisense oligonucleotides that are capable of modulating expression of Tau in a target cell. The oligonucleotides hybridize to MAPT mRNA. The present invention further relates to conjugates of the oligonucleotide and pharmaceutical compositions and methods for treatment of Tauopathies, Alzheimzer's disease, fronto-temporal dementia (FTD), FTDP-17, progressive supranuclear palsy (PSP), chronic traumatic encephalopathy (CTE), corticobasal ganglionic degeneration (CBD), epilepsy, Dravet syndrome, depression, seizure disorders and movement disorders.

The present disclosure provides a DNA-targeting RNA that comprises a targeting sequence and, together with a modifying polypeptide, provides for site-specific modification of a target DNA and/or a polypeptide associated with the target DNA. The present disclosure further provides site-specific modifying polypeptides. The present disclosure further provides methods of site-specific modification of a target DNA and/or a polypeptide associated with the target DNA The present disclosure provides methods of modulating transcription of a target nucleic acid in a target cell, generally involving contacting the target nucleic acid with an enzymatically inactive Cas9 polypeptide and a DNA-targeting RNA. Kits and compositions for carrying out the methods are also provided. The present disclosure provides genetically modified cells that produce Cas9; and Cas9 transgenic non-human multicellular organisms.

The present disclosure provides a DNA-targeting RNA that comprises a targeting sequence and, together with a modifying polypeptide, provides for site-specific modification of a target DNA and/or a polypeptide associated with the target DNA. The present disclosure further provides site-specific modifying polypeptides. The present disclosure further provides methods of site-specific modification of a target DNA and/or a polypeptide associated with the target DNA The present disclosure provides methods of modulating transcription of a target nucleic acid in a target cell, generally involving contacting the target nucleic acid with an enzymatically inactive Cas9 polypeptide and a DNA-targeting RNA. Kits and compositions for carrying out the methods are also provided. The present disclosure provides genetically modified cells that produce Cas9; and Cas9 transgenic non-human multicellular organisms.

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.