Targeting of repeated sequences unique to a gene results in significant increases in antisense oligonucleotide potency.

ABSTRACT: A new strategy for identifying potent RNase H-dependent antisense oligonucleotides (ASOs) is presented. Our analysis of the human transcriptome revealed that a significant proportion of genes contain unique repeated sequences of 16 or more nucleotides in length. Activities of ASOs targeting these repeated sites in several representative genes were compared to those of ASOs targeting unique single sites in the same transcript. Antisense activity at repeated sites was also evaluated in a highly controlled minigene system. Targeting both native and minigene repeat sites resulted in significant increases in potency as compared to targeting of non-repeated sites. The increased potency at these sites is a result of increased frequency of ASO/RNA interactions which, in turn, increases the probabi

SUBMITTER: Vickers TA 

PROVIDER: S-EPMC4198294 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature