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injection of different antimi Rs as indicated±light activation in vivo. The in vivo activation of caged antimi R-92a leads to a significant reduction of mi R-92a levels in the murine skin with an efficiency that is comparable to constitutively active antimi R-92a, while the controls have no effects (Fig. Additionally, by measuring mi R-92a level in the kidney and liver, we show that locally light-activated antimi R-92a does not significantly affect the kidney or liver mi R-92a levels (Fig. These data demonstrate that caged antimi Rs can be successfully activated by light in vivo.
1a).(a) mi R-92a expression level quantified by real-time PCR in skin explants after 48 h of intradermal injection with different antimi Rs as indicated±light activation ex vivo. Antimi Rs were composed of 2′-OMe-modified nucleotides and contained in total six phosphorothioates at the 3′- and 5′-end to allow stability against endonucleases and exonucleases.
Here we show that light-activatable antimi Rs efficiently and locally restricted target mi R activity in vivo.
We use an antimi R-92a and establish a therapeutic benefit in diabetic wound healing.
Therefore, we measured mi R-92a level in acute wounds from Bl/6 wild-type mice and healing-impaired diabetic wounds from db/db mice (time points were chosen in accordance with the estimated peak of angiogenesis) as well as in acute human wound tissue and from non-healing human venous leg ulcers.
These analysis revealed that mi R-92a is strongly upregulated in chronic wounds in comparison to acute wounds, indicating that mi R-92a may represent a therapeutic target to rescue impaired chronic wound healing (Fig.