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Light-activatable antimiRs efficiently and locally restrict target miR activity in vivo

May 2017. 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. A team of scientists led by Stefanie Dimmeler from the Goethe University Frankfurt demonstrates that light-activatable antimiRs efficiently and locally restricted target miR activity in vivo. The scientists 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. More ...

Contact:
Stefanie Dimmeler, Institute of Cardiovascular Regeneration, Centre for Molecular Medicine, Goethe-University Frankfurt, Frankfurt/Main, Germany, dimmeler@em.uni-frankfurt.de

Publication:
Lucas T, Schäfer F, Müller P, Emig S, Heckel A, Dimmeler S (2017) Light-inducible antimiR-92a as a therapeutic strategy to promote skin repair in healing-impaired diabetic mice. Nature Communications: 183814. 10.1038/ncomms15162. Link...

 

Cluster of Excellence Macromolecular Complexes, Frankfurt am Main, Germany