Chemical modification of short small hairpin RNAs for inhibition of gene expression

A small hairpin RNA (shRNA) consisting essentially of:

• (a) a sense sequence consisting of 11 to 18 ribonucleotides;
• (b) an antisense sequence consisting of 16 to 19 ribonucleotides, wherein the ribonucleotides consist of one or more modified ribonucleotides and unmodified ribonucleotides, wherein the one or more modified ribonucleotides of the antisense sequence are at a position selected from one or more of position 2, 15, 16, 17, 18, and 19 from the 5′ end of the antisense sequence;
• wherein the antisense sequence is substantially complementary to the sense sequence;
• (c) a loop region connecting the 3′ end of the antisense sequence to the 5′ end of the sense sequence, and
• (d) an optional 5′ overhang or a 3′ overhang of at least one ribonucleotide, wherein the 5′ end of the antisense sequence and the 3′ end of the sense sequence are not connected by an internucleotide linkage.