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.

This invention relates to compounds, compositions, and methods useful for reducing KRAS target RNA and protein levels via use of Dicer substrate siRNA (DsiRNA) agents possessing asymmetric end structures.

The present application describes structures, systems, and methods for modeling and analysis of single-strand break (SSB) signaling and repair in a cell-free system. Also provided are methods of making the SSB structures and SSB signaling and repair systems. Methods and systems for identifying modulators of DNA damage response (DDR) activity for SSB repair are also described as well as methods of inhibiting SSB repair.

A recombinant viral vector comprising an expression cassette which comprises a coding sequence for an shRNA inhibitor of vasohibin (VASH)-small vasohibin binding protein (SVBP) complex operably linked to regulatory sequences which direct expression thereof is provided. Further provided are compositions containing such viral vectors formulated for delivery to a human patient. Also provided are methods using these vectors and compositions for improving or stabilizing cardiac function.

Provided herein are compositions and methods that can be utilized to ameliorate, treat, or at least partially eliminate diseases and conditions that can arise from genomic mutations. Subject compositions and methods can be used to edit RNA to ameliorate, treat, or at least partially eliminate the disease and conditions in a subject.

The invention provides compositions and methods of making and using effector oligonucleotides, including effector oligonucleotides with greater than one mismatch as compared to its target sequence. These effector oligonucleotides are useful for improving the efficiency of genomic editing as well as providing therapeutic benefits to individuals in need thereof.

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.

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.

This invention relates to compounds, compositions, and methods useful for reducing AT3 target RNA and protein levels via use of dsRNAs, e.g., Dicer substrate siRNA (DsiRNA) agents.

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.