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

Nat Commun. 2017 May 2;8:15162. doi: 10.1038/ncomms15162.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antagomirs / administration & dosage
  • Antagomirs / genetics*
  • Antagomirs / metabolism
  • Diabetes Mellitus, Experimental / genetics
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology
  • Gene Expression Regulation
  • Humans
  • Injections, Intradermal
  • Integrin alpha5 / genetics
  • Integrin alpha5 / metabolism
  • Kidney / metabolism
  • Light
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / antagonists & inhibitors*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Neovascularization, Physiologic / genetics
  • Neovascularization, Physiologic / radiation effects*
  • Organ Specificity
  • Photochemical Processes
  • Signal Transduction
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism
  • Skin / blood supply
  • Skin / injuries
  • Skin / metabolism
  • Skin / radiation effects*
  • Wound Healing / genetics
  • Wound Healing / radiation effects*
  • Wounds, Nonpenetrating / genetics
  • Wounds, Nonpenetrating / metabolism
  • Wounds, Nonpenetrating / pathology
  • Wounds, Nonpenetrating / therapy*

Substances

  • Antagomirs
  • Integrin alpha5
  • MicroRNAs
  • Mirn92 microRNA, mouse
  • Sirt1 protein, mouse
  • Sirtuin 1