@ ETH, Switzerland; The University of Manchester, UK
miRNAs as new regulators of regeneration
Many patients suffer from insufficient wound healing following injuries, large-area burns, chronic diabetic sores, and aging skin fragility. The development of efficient strategies for the improvement of cutaneous repair requires understanding of the mechanisms underlying normal and impaired wound healing. Many factors can interfere with one or more phases of the cutaneous healing process, thus causing improper or impaired wound healing in patients. Recent data implicates microRNAs (miRs) as one such factor involved in wound repair. Because of the short sequence (~20 nt) and the tissue-specific activity, miRs are targets for oligonucleotide-based RNA silencing therapy. The accessibility of the skin allows local miR manipulation. Our previous work identified an important function of miR-29s in regulating desmosomes in normal and hyper-proliferative epidermis. miR-29s also regulate collagen production by fibroblasts and are a new therapeutic target in the Phase I clinical trial for cutaneous sclerosis. However, the regulation and functions of miR-29s in homeostatic and regenerating epidermis remain largely unknown. The in vivo function of miRs depends on the tissue-specific expression of RNA targets. We are using fluorescently labeled miR-29 antisense oligonucleotides with enhanced in vivo activity to track their delivery into wounds, and test the ability of antisense miR-29s to improve cutaneous wound healing. The results of this project will help developing a new miR-based approach for treatment of cutaneous wounds. In addition, it will open new avenues for the use of modified antisense oligonucleotides as a therapy for non-healing wounds and other types of skin diseases.