US Patent 6846921 Chimeric antisense oligonucleotides and cell transfecting formulations thereof

Chimeric oligonucleotide of the formula 5′-W—X1—Y—X2—Z-3′, where W represents a 5′-O-alkyl nucleotide, each of X1 and X2 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 formulaL-linker-[N(CH2CH2NH2)CH2(C═O)—N(CH2CH2R)CH2(C═O)—N(CH2CH2R)CH2(C═O)]3—NH2,where L is a lipid moiety, including a steroid, and each group R is independently selected from alkyl, aminoalkyl, and aralkyl.