4 years ago

Light-inducible antimiR-92a as a therapeutic strategy to promote skin repair in healing-impaired diabetic mice

Light-inducible antimiR-92a as a therapeutic strategy to promote skin repair in healing-impaired diabetic mice
Patricia Müller, Tina Lucas, Sabine A. Eming, Florian Schäfer, Stefanie Dimmeler, Alexander Heckel
MicroRNAs (miRs) are small non-coding RNAs that post-transcriptionally control gene expression. Inhibition of miRs by antisense RNAs (antimiRs) might be a therapeutic option for many diseases, but systemic inhibition can have adverse effects. Here we show that light-activatable antimiRs efficiently and locally restricted target miR activity in vivo. We use an antimiR-92a and establish a therapeutic benefit in diabetic wound healing. AntimiR-92a is modified with photolabile protecting groups, so called ‘cages’. Irradiation activates intradermally injected caged antimiR-92a without substantially affecting miR-92a expression in other organs. Light activation of caged antimiR-92a improves healing in diabetic mice to a similar extent as conventional antimiRs and derepresses the miR-92a targets Itga5 and Sirt1, thereby regulating wound cell proliferation and angiogenesis. These data show that light can be used to locally activate therapeutically active antimiRs in vivo.

Publisher URL: http://www.nature.com/articles/ncomms15162

DOI: 10.1038/ncomms15162

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