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Harnessing Adeno Associated Virus (AAV) technology for the treatment of scarring
Harnessing Adeno Associated Virus (AAV) technology for the treatment of scarring
Deep skin wounds rapidly heal with scars and contractures by mobilizing extracellular matrix and cells from the fascia, deep beneath the dermal layer of the skin. Here, we demonstrate that Adeno-associated virus 8 (AAV8) is highly effective for transducing scar-forming fibroblasts in the fascia. p120 is up-regulated explicitly in scar-forming fibroblasts populations in response to injury. We demonstrate in animals that AAV8 mediated short hairpin RNA (ShRNA) silencing of p120, specifically in the fascia, reduces extracellular matrix (ECM) mobilization and enables scarless wound repair outcomes. Our findings demonstrate the potential for specifically targeting mechanisms of fascia mobilization with AAV8 vectors and the translational applications of this technology in modulating endogenous repair responses to restore the function of injured tissues in a scarless fashion.
Skin, Scar, p120, AAV, Fascia, Fibroblasts
Rajendran, Vijayanand
2022
Englisch
Universitätsbibliothek der Ludwig-Maximilians-Universität München
Rajendran, Vijayanand (2022): Harnessing Adeno Associated Virus (AAV) technology for the treatment of scarring. Dissertation, LMU München: Medizinische Fakultät
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Abstract

Deep skin wounds rapidly heal with scars and contractures by mobilizing extracellular matrix and cells from the fascia, deep beneath the dermal layer of the skin. Here, we demonstrate that Adeno-associated virus 8 (AAV8) is highly effective for transducing scar-forming fibroblasts in the fascia. p120 is up-regulated explicitly in scar-forming fibroblasts populations in response to injury. We demonstrate in animals that AAV8 mediated short hairpin RNA (ShRNA) silencing of p120, specifically in the fascia, reduces extracellular matrix (ECM) mobilization and enables scarless wound repair outcomes. Our findings demonstrate the potential for specifically targeting mechanisms of fascia mobilization with AAV8 vectors and the translational applications of this technology in modulating endogenous repair responses to restore the function of injured tissues in a scarless fashion.