Role of Extracellular Vesicles, Modified mRNA, miRNA, and siRNA in Diabetic Lower Extremity Complications

Diabetic foot ulcers (DFUs) are a global health concern that requires urgent attention, given the projected increase in the diabetic population. These non-healing ulcers often become infected and can ultimately result in amputation. In an effort to enhance healing outcomes, gene therapy has emerged as a promising alternative to conventional treatments such as bioengineered materials/tissues or growth factors. RNA-based therapeutic approaches, including siRNA, miRNA, and mRNA, have shown remarkable potential in addressing chronic wounds in various preclinical models and human clinical trials. To optimize the delivery of target RNA, researchers have primarily focused on nucleic acid delivery nano-carriers (such as extracellular vesicles and lipid nanoparticles) and RNA modification techniques (including chemically modified nucleobases and ligand conjugation). In this chapter, our focus is on the recent advancements in the development of extracellular vesicles and RNA-based therapeutics, as well as ongoing research related to genes that play a crucial role in the processes of chronic wound healing.