The present invention relates to specific reverse micelle system of the invention which allows the administration and intracellular delivery of unmodified oligonucleotide, such as siRNA, targeting one or more genes of the SARS-CoV-2 virus. The reverse micelle system of the invention is thus particularly useful for the treatment of the viral pathology linked to the SARS-CoV-2 virus.

Provided herein are self-delivering oligonucleotides that are characterized by efficient RISC entry, minimum immune response and off-target effects, efficient cellular uptake without formulation, and efficient and specific tissue distribution.

The present disclosure provides DNA-guided CRISPR systems; polynucleotides comprising DNA, RNA and mixtures thereof for use with CRISPR systems; and methods of use involving such polynucleotides and DNA-guided CRISPR systems.

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.

Chemically modified Neisseria meningitidis (Nme) crRNAs, tracrRNAs, and sgRNAs are provided. Methods of using the Nme crRNAs, tracrRNAs, and sgRNAs for genome editing with a Nme CRISPR nuclease and kits for performing the same are also provided.

The present invention relates to RNAi constructs and their use in gene silencing. RNAi constructs associated with the invention contain a double stranded region connected to a single stranded region of phosphorothioate modified nucleotides.

The present disclosure relates to RNA amidates and thioamidates useful for RNA interference applications. The RNA amidates and thioamidates contain at least one internucleoside linkage chosen from ribo-N3′.fwdarw.P5′ phosphoramidate (NP) and ribo-N3′.fwdarw.P5′ thiophosphoramidate (NPS) linkages, and optionally further containing at least one covalently conjugated lipid moiety. Compositions comprising the amidates and thioamidates are disclosed, as are methods for their use in modulating gene expression.

The invention relates to synthetic plant miRNA precursor molecules that are resistant to processing in plants but functional in plant pests. The invention further relates to methods for using the synthetic plant miRNA precursor molecules to protect plants against pests.

The present invention provides a novel siRNA specifically inhibiting the expression of IL-23 and a pharmaceutical composition comprising the siRNA, specifically a double stranded RNA comprising a sense strand and an antisense strand wherein each strand has 19 to 30 nucleotides and comprises the base sequence selected from SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 or SEQ ID NO: 6 or a complementary base sequence thereof and a pharmaceutical composition comprising the double stranded RNA.

This disclosure relates to novel huntingtin targets. Novel oligonucleotides for the treatment of Huntington's disease are also provided.