Non-Viral Modulation of Cutaneous Tissue Plasticity as a Therapy for Diabetes

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PROJECT SUMMARY In vivo reprogramming has the potential to facilitate the development of highly promising and translational personalized cell therapies for a wide variety of conditions. Current reprogramming methodologies, however, face major practical and translational hurdles, including heavy reliance on viral transfection, and a highly stochastic nature, which often leads to inefficient and/or unpredictable reprogramming outcomes. We developed a novel nanotechnology-based approach that overcomes these barriers by enabling deterministic transduction of reprogramming factors into tissues with single-cell resolution and without the need for viral vectors. Tissue Nano-Transfection (TNT) promotes remarkably fast and efficient direct cellular reprogramming in vivo. Such platform technology could be applicable to virtually any reprogramming model, and its non-invasive and non- viral nature make it an ideal candidate for use in highly complex disease systems, such as diabetes. This application will focus on developing TNT-driven strategies to enable paradigm-shifting cell therapies for diabetes, obesity, and other metabolic disorders; by “repurposing” portions of the skin to serve a therapeutic purpose (e.g., sense glucose and release insulin accordingly). As such, the work proposed herein is fundamentally innovative and potentially transformative.