| abstract |
Chimeric oligonucleotide of the formula 5′-W-X 1 -Y-X 2 -Z-3′, where W represents a 5′-O-alkyl nucleotide, each of X 1 and X 2 represents a block of seven to twelve phosphodiester-linked 2′-O-alkyl ribonucleotides, Y represents a block of five to twelve phosphorothioate-linked deoxyribonucleotides, and Z represents a blocking group effective to block nuclease activity at the 3′ end of the oligonucleotide, are described. These compounds exhibit high resistance to endo- and exonucleases, high sequence specificity, and the ability to activate RNAse H, as evidenced by efficient and long-lasting suppression of target mRNA. The oligonucleotides are preferably transfected into cells in formulations containing a lipid-peptoid conjugate carrier molecule of the formula n L-linker-[N(CH 2 CH 2 NH 2 )CH 2 (C═O)-N(CH 2 CH 2 R)CH 2 (C═O)—N(CH 2 CH 2 R)CH 2 (C═O)] 3 -NH 2 , n where L is a lipid moiety, including a steroid, and each group R is independently selected from alkyl, aminoalkyl, and aralkyl. |