The small molecule Retro-1 enhances the pharmacological actions of antisense and splice switching oligonucleotides.

ABSTRACT: The attainment of strong pharmacological effects with oligonucleotides is hampered by inefficient access of these molecules to their sites of action in the cytosol or nucleus. Attempts to address this problem with lipid or polymeric delivery systems have been only partially successful. Here, we describe a novel alternative approach involving the use of a non-toxic small molecule to enhance the pharmacological effects of oligonucleotides. The compound Retro-1 was discovered in a screen for small molecules that reduce the actions of bacterial toxins and has been shown to block the retrograde trafficking pathway. We demonstrate that Retro-1 can also substantially enhance the effectiveness of antisense and splice switching oligonucleotides in cell culture. This effect occurs at the level of in

SUBMITTER: Ming X 

PROVIDER: S-EPMC3616695 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature