| 摘要 |
Disclosed is a compound comprising a modified oligonucleotide consisting of 16 to 22 linked nucleosides, wherein the nucleobase sequence of the modified oligonucleotide is complementary to miR-21 (SEQ ID NO: 1) and wherein the modified oligonucleotide comprises at least 16 contiguous nucleosides of the following nucleoside pattern I in the 5’ to 3’ orientation: (R)X-NB-NQ-NQ-NB-(NQ-NQ-NQ-NB)3-NQ-NZ wherein each R is, independently, a non-bicyclic nucleoside; X is from 1 to 4; each NB is, independently, a bicyclic nucleoside; each NQ is, independently, a non-bicyclic nucleoside; and NZ is a modified nucleoside, and wherein (i) each bicyclic nucleoside comprises a non-methylated nucleobase, or (ii) no more than two non-bicyclic nucleosides are 2’-O-methoxyethyl nucleosides and each other non-bicyclic nucleoside is a &bgr;-D-deoxyribonucleoside. Also disclosed is a compound comprising a modified oligonucleotide consisting of 16 to 19 linked nucleosides, wherein the nucleobase sequence of the modified oligonucleotide is complementary to miR-21 (SEQ ID NO: 1) and wherein the modified oligonucleotide comprises at least 16 contiguous nucleosides of the following nucleoside pattern III in the 5’ to 3’ orientation: (R)X-NB-NQ-NQ-NB-(NQ-NQ-NQ-NB)3-NY-NZ wherein each R is a non-bicyclic nucleoside; X is from 1 to 4; each NB is a bicyclic nucleoside; each NQ is a non-bicyclic nucleoside; NY is a modified nucleoside or an unmodified nucleoside; and NZ is a modified nucleoside, and wherein (i) each bicyclic nucleoside comprises a non-methylated nucleobase, or (ii) no more than two non-bicyclic nucleosides are 2’-O-methoxyethyl nucleosides and each other non-bicyclic nucleoside is a &bgr;-D-deoxyribonucleoside. Also disclosed is the use of the above-described compounds in the manufacture of a medicament for decreasing collagen expression in a cell, wherein the medicament is to be contacted to a cell. |
