FPR2 DNA Aptamers for Targeted Therapy of Wound Repair

Abstract

Chronic wounds represent a major health problem worldwide. Some of the available therapies based on recombinant proteins usually fail owing to the hostile environment found at the wound bed. Aptamers appear as an attractive alternative to recombinant factors owing in part to their stability, sensitivity, specificity, and low-cost production. In this study, the Cell-Systematic Evolution of Ligands by EXponential Enrichment technology was employed to generate aptamers that specifically recognize and modulate the function of the FPR2, a receptor expressed in a variety of cells involved in wound repair. Three aptamers were obtained that specifically bound to FPR2 stable transfectants generated in HaCaT cells. The targeted aptamers were shown to act as FPR2 agonists in different invitro functional assays, including wound healing assays, and elicited a similar pattern of response to that obtained with other known FPR2 peptide agonists, such as the human LL37 cathelicidin. We have also obtained invivo evidence for the prohealing activities of one of these FPR2 aptamers in a skin-humanized mouse model developed by us, previously shown to accurately recreate the main phases of physiological human wound repair process. In conclusion, we provide evidence of the potential therapeutic value of FPR2 aptamers for cutaneous repair.