| 摘要 |
PROBLEM TO BE SOLVED: To provide gapmer antisense compounds for reduction of target RNA in vivo comprising different nucleotide modifications within one or both wing regions, which include high-affinity bicyclic nucleotide modifications but are designed to have mitigated toxicity by incorporation of non-bicyclic high-affinity modified nucleotides.SOLUTION: An oligomeric compound comprises a gapmer oligonucleotide consisting of 10 to 25 linked nucleosides. The gapmer oligonucleotide has a 5' wing region positioned at the 5' end of a deoxynucleotide gap, and a 3' wing region positioned at the 3' end of the deoxynucleotide gap. At least one nucleoside of at least one of the wing regions is a 4' to 2' bicyclic nucleoside, and at least one of the remaining wing nucleosides is a non-bicyclic 2'-modified nucleoside. |
