Inhibition of bcl-xL expression by antisense oligonucleotides containing various bridged nucleic acids (BNAs).

Abstract

Recently, we described the antisense activity of 2',4'-BNA oligonucleotides in living cells.(1) Here, we examine the antisense effect of 2',4'-BNA, 2',4'-(COC) and 3'-amino-2',4'-BNA oligonucleotides targeting the bcl-xL gene. The results showed that while S-oligo had a slightly inhibiting effect on bcl-xL expression and natural DNA had no effect, an antisense oligonucleotide (AON) containing six 2',4'-(COC) nucleotides reduced the bcl-xL mRNA level to 64% of the untreated level. Interestingly, several types of AON-those containing nine 2',4'-BNA(COC) nucleotides, 2',4'-BNA and 3'-amino-2',4'-BNA- completely inhibited expression of the target gene. These data show that, compared with the corresponding natural DNA and S-oligo, BNA-based AONs are efficient inhibitors of bcl-xL expression.