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Improving Wound Healing with Topical Gene Therapy.

BACKGROUND
Impaired wound healing remains a major clinical problem with many etiologies. Altering gene expression to enhance healing is an innovative therapeutic approach. In recent years, we have developed a means to topically silence genes at the post-transcriptional level to locally alter wounds and improve the healing process.


THE PROBLEM
Many types of chronic wounds have been associated with alterations in the expression of genes that mediate healing. Targeting the expression of these genes in a way that can improve healing while limiting systemic side effects has been very challenging.


BASIC/CLINICAL SCIENCE ADVANCES
Our laboratory's recent work has focused on the use of topically applied small interfering ribonucleic acid (siRNA) to inhibit messenger RNA expression of certain mediators involved in healing in two different types of cutaneous injury-radiation-induced cutaneous injury and the diabetic excisional wound. By successfully inhibiting specific gene mediators with topical siRNA, we reversed downstream signaling pathways, which led to expedited wound healing in diabetic wounds and restoration to a more normal phenotype in radiation-induced skin injuries.


CLINICAL CARE RELEVANCE
The signaling pathways and gene mediators that we targeted and inhibited in murine models are present in humans. Applying parallel treatment strategies in humans may provide novel means of treating these burdensome and costly conditions.


CONCLUSION
Our novel method for local gene silencing is effective in treating various types of cutaneous murine wounds. Topical gene silencing with siRNA obviates the side effects of systemic medication and has the potential to be effective in healing or preventing a wide array of cutaneous human conditions.