Identifying and avoiding off-target effects of RNase H-dependent antisense oligonucleotides in mice.

ABSTRACT: Antisense oligonucleotides that are dependent on RNase H for cleavage and subsequent degradation of complementary RNA are being developed as therapeutics. Besides the intended RNA target, such oligonucleotides may also cause degradation of unintended RNA off-targets by binding to partially complementary target sites. Here, we characterized the global effects on the mouse liver transcriptome of four oligonucleotides designed as gapmers, two targeting Apob and two targeting Pcsk9, all in different regions on their respective intended targets. This study design allowed separation of intended- and off-target effects on the transcriptome for each gapmer. Next, we used sequence analysis to identify possible partially complementary binding sites among the potential off-targets, and validated thes

SUBMITTER: Hagedorn PH 

PROVIDER: S-EPMC6009603 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature