Asymmetric Short Duplex RNA with Interspersed Deoxyribonucleotides as a Gene Silencing Technology and Use Thereof

An asymmetric short duplex RNA (asdRNA) molecule comprising a first strand and a second strand each comprising linked ribonucleotide monomers with at least one interspersed segment of deoxyribonucleotide monomer(s) (ISD) disposed in the first strand,

• wherein the ribonucleotide monomer is selected from the group consisting of a naturally occurring ribonucleotides, an analog thereof, and a modified ribonucleotide;
• and the deoxyribonucleotide monomer is selected from the group consisting of a naturally occurring deoxyribonucleotide, an analog thereof, and a modified deoxyribonucleotide;
• wherein at least one ISD comprises at least 2, 3, 4, 5, 6, 7, 8, 9 or 10 contiguous deoxyribonucleotide monomers;
• wherein the second strand is shorter than the first strand by a number of monomers selected from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 monomers;
• wherein the first strand is substantially complementary to a targeted segment of a targeted RNA through at least one targeting region, and wherein the first strand consists of 10-36 (both range endpoints included) nucleoside monomers linked through a linkage selected from the group consisting of a phosphorothioate linkage, a phosphodiester linkage, or a mixture of phosphorothioate and phosphodiester linkages between adjacent monomers;
• wherein the second strand is substantially complementary to the first strand, and forms at least one double-stranded region with the first strand, and wherein the second strand consists of 8-32 (both range endpoints included) nucleoside monomers linked through a linkage selected from the group consisting of a phosphorothioate linkage, a phosphodiester linkage, or a mixture of phosphorothioate and phosphodiester linkages between adjacent monomers;
• and
• wherein the total number of deoxyribonucleotide monomer(s) is no more than the total number of ribonucleotide monomers in the asdRNA molecule.