Reduction of Off-Target Effects of Gapmer Antisense Oligonucleotides by Oligonucleotide Extension.

ABSTRACT:

Aim

Antisense oligonucleotide (ASO) has the potential to induce off-target effects by inadvertent binding of ASOs to unintended RNAs that have a sequence similar to the target RNA. In the present study, we focused on the association between oligonucleotide length and off-target effects. Oligonucleotide extension is assumed to have bilateral effects on hybridization-dependent changes in gene expression, i.e., one is the decrease of off-target effects based on the reduced number of off-target candidate genes with perfect matches, and the other is the increase of off-target effects based on the increased binding affinity between the ASO and the complementary RNAs that leads to better tolerability for mismatches.

Methods

To determine the effects of oligonucleotide extension of g

SUBMITTER: Yasuhara H 

PROVIDER: S-EPMC8766371 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature