The present invention relates to RNAi molecules, and compositions thereof, comprising a 2 internucleoside linkage connecting the nucleotide at position 1 and the nucleotide at position 2 at the 5 end of the antisense strand. Specifically, the invention relates to single- and double-stranded short interfering nucleic acid (siNA) molecules that are capable of mediating RNA interference comprising 5 modified nucleotides that comprise, among other potential modifications, a 2 internucleoside linkage. The invention further relates to 5 modified nucleotides used as reagents to generate the RNAi molecules of the invention and methods of using the disclosed RNAi molecules.

The present application relates to nucleic acid compounds, compositions comprising same and methods of use thereof for treatment of various diseases, disorders and conditions. The compounds are preferably chemically synthesized and modified double-stranded nucleic acid molecules which down regulate expression of a p53 gene.

Modification formats having modified nucleotides are provided for siRNA. Short interfering RNA having modification formats and modified nucleotides provided herein reduce off-target effects in RNA interference of endogenous genes. Further modification formatted siRNAs are demonstrated to be stabilized to nuclease-rich environments. Unexpectedly, increasing or maintaining strand bias, while necessary to maintain potency for endogenous RNA interference, is not sufficient for reducing off-target effects in cell biology assays.

The present invention relates to RNAi molecules, and compositions thereof, comprising a 2 internucleoside linkage connecting the nucleotide at position 1 and the nucleotide at position 2 at the 5 end of the antisense strand. Specifically, the invention relates to single- and double-stranded short interfering nucleic acid (siNA) molecules that are capable of mediating RNA interference comprising 5 modified nucleotides that comprise, among other potential modifications, a 2 internucleoside linkage. The invention further relates to 5 modified nucleotides used as reagents to generate the RNAi molecules of the invention and methods of using the disclosed RNAi molecules.

The present application relates to nucleic acid compounds, compositions comprising same and methods of use thereof for treatment of various diseases, disorders and conditions. The compounds are preferably chemically synthesized and modified double-stranded nucleic acid molecules which down regulate expression of a p53 gene.

The invention, in some embodiments, relates to compounds and methods for the prevention of ischemia reperfusion injury (IRI) in organs, and in particular to IRI in organs aged 35 years and older. Specific uses include prevention of IRI in native organs in vivo, in reimplantations and in transplantations of donor organs aged 35 years and older. Additional embodiments include the prophylaxis of delayed graft function (DGF) and reduction in the frequency, amount and duration of dialysis in recipients of deceased donor kidney transplantations. The methods entail contacting the organ in vivo or ex vivo with a temporary p53 inhibitor. Novel temporary dsNA p53 inhibitors are further provided.

The invention, in some embodiments, relates to compounds and methods for the prevention of ischemia reperfusion injury (IRI) in organs, and in particular to IRI in organs aged 35 years and older. Specific uses include prevention of IRI in native organs in vivo, in reimplantations and in transplantations of donor organs aged 35 years and older. Additional embodiments include the prophylaxis of delayed graft function (DGF) and reduction in the frequency, amount and duration of dialysis in recipients of deceased donor kidney transplantations. The methods entail contacting the organ in vivo or ex vivo with a temporary p53 inhibitor. Novel temporary dsNA p53 inhibitors are further provided.

Provided herein are double stranded nucleic acid molecules, compositions comprising same and methods of use thereof for the treatment of a subject wherein expression of DDIT4 is associated with the etiology or progression of a disease or disorder in the subject. The compounds are preferably chemically synthesized and modified dsRNA molecules.

The invention, in some embodiments, relates to compounds and methods for the prevention of ischemia reperfusion injury (IRI) in organs, and in particular to IRI in organs aged 35 years and older. Specific uses include prevention of IRI in native organs in vivo, in reimplantations and in transplantations of donor organs aged 35 years and older. Additional embodiments include the prophylaxis of delayed graft function (DGF) and reduction in the frequency, amount and duration of dialysis in recipients of deceased donor kidney transplantations. The methods entail contacting the organ in vivo or ex vivo with a temporary p53 inhibitor. Novel temporary dsNA p53 inhibitors are further provided.

The present invention relates, in general to agents that modulate the pharmacological activity of conjugated siRNAs.