Reduced size self-delivering RNAi compounds

A method comprising:

• administering to a subject having a tumor an sd-rxRNA® in an effective amount to promote RNA interference by the sd-rxRNA® in the tumor, wherein the sd-rxRNA® comprises a guide strand and a passenger strand, wherein the sd-rxRNA® includes a double-stranded region and a single stranded region wherein the double stranded region is from 8-15 nucleotides long, wherein the single stranded region is at the 3′ end of the guide strand and is 4-12 nucleotides long, wherein the single stranded region contains 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 phosphorothioate modifications, and wherein at least 40% of the nucleotides of the sd-rxRNA® are modified, and wherein at least two Us and/or Cs include a hydrophobic modification selected from the group consisting of a thiophene, octyn-1-yl, and ethynyl modification, located on position 5 of the Us and/or Cs.

A method comprising:

• administering an sd-rxRNA® to the central nervous system of a subject in need thereof, wherein the sd-rxRNA® comprises a guide strand and a passenger strand, wherein the sd-rxRNA® includes a double-stranded region and a single stranded region wherein the double stranded region is from 8-15 nucleotides long, wherein the single stranded region is at the 3′ end of the guide strand and is 4-12 nucleotides long, wherein the single stranded region contains 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 phosphorothioate modifications, and wherein at least 40% of the nucleotides of the sd-rxRNA® are modified, and wherein at least two Us and/or Cs include a hydrophobic modification selected from the group consisting of a thiophene, octyn-1-yl, and ethynyl modification, located on position 5 of the Us and/or Cs.

A method for delivering a nucleic acid to a remote target tissue in a subject in need thereof, comprising

• systemically administering to the subject an sd-rxRNA® in an effective amount to promote RNA interference by the sd-rxRNA® in the remote target tissue, wherein the sd-rxRNA® comprises a guide strand and a passenger strand, wherein the sd-rxRNA® includes a double-stranded region and a single stranded region wherein the double stranded region is from 8-15 nucleotides long, wherein the single stranded region is at the 3′ end of the guide strand and is 4-12 nucleotides long, wherein the single stranded region contains 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 phosphorothioate modifications, wherein at least 40% of the nucleotides of the sd-rxRNA® are modified, wherein at least two Us include an imidazole modification, and wherein the imidazole modifications are located on position 5 of the Us.