Regulating Angiogenesis with Light‐Inducible AntimiRs

Abstract

The inhibition of microRNAs (miRs) in a spatiotemporally defined manner by an exogenous trigger would help to specifically target the biological activity and avoid off-target effects. Novel antimiRs directed against miR-92a can be activated by irradiation (see scheme; 3'-UTR=3'-untranslated region) In this way miR-92a is inhibited, the miR-92a target integrin α5 is derepressed, and angiogenesis of endothelial cells is enhanced.

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

“…Since wavelengths of this range can effectively remove photolabile-protecting groups10 but are not expected to induce direct photo damage as compared to shorter wavelengths of the ultraviolet spectrum, light of 385 nm was used for the subsequent experiments. Caged antimiR-92a, developed in earlier studies10, was injected intradermally into murine skin explants (1 μg diluted in 50 μl PBS). After irradiation for 10 min (385 nm, 300 mA) and subsequent cultivation for 48 h, levels of miR-92a were analysed by quantitative real-time PCR.…”

“…Several targeting strategies have been experimentally used including the linking of miRs or antimiRs to aptamers45, nanoparticle- or microparticle-mediated delivery67 and cell type-specific delivery by viral vectors8 as well as attempts of local delivery by mechanical tools, for example, catheters9. In addition, we and others have developed photoactivatable antimiRs by attaching photolabile protecting groups (cages) to the nucleobases that temporarily inhibit duplex formation with the target miR, thereby allowing an excellent on/off behaviour upon irradiation10111213. However, the therapeutic in vivo use of light-activatable antimiRs has been unclear.…”

Red light activated “caged” reagents for microRNA research

“…9 In contrast to numerous examples of "caged" miRNA inhibitors, a single report describing "caged" miRNA mimics is available: Dmochowski and co-workers have synthesized "caged" mimics of let7 miRNA by covalent linking its 3′-and 5′-termini via a photocleavable moiety. The resulting inactive circular RNAs could be activated in zebrafish embryos by their exposure to 365 nm light.…”

RNA Therapeutics for Treatment of Cardiovascular Diseases

“…Alternative strategies may include local activation of anti-miRs by light, as it was shown in first proof-of-concept studies in primary human endothelial cells. 9 But its feasibility in inlying organs, such as the heart, needs to be studied.…”