Inhibition of bcl-xL expression by antisense oligonucleotides containing various bridged nucleic acids (BNAs).
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.
Roongjang
Somjing
S
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
Takahashi
Kurena
K
Obika
Satoshi
S
Imanishi
Takeshi
T
D001952:Bridged-Ring Compounds / Q000737:chemistry; D045744:Cell Line, Tumor; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000737:chemistry* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051020:bcl-X Protein / Q000037:antagonists & inhibitors* / Q000235:genetics
C494811:BCL2L1 protein, human; D001952:Bridged-Ring Compounds; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D051020:bcl-X Protein