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.
Although in vivo cell reprogramming could enable the development of highly promising cell therapies against diabetes, status quo methodologies face multiple practical and translational hurdles. So as to overcome these barriers, we propose to use a novel platform nanotechnology, Tissue Nano-Transfection (TNT), to develop novel reprograming-based strategies that can enable highly transformational ? cell replacement and thermogenic cell therapies of interest to diabetes, obesity, and other metabolic disorders. Diabetes affects millions of patients worldwide, and with >350 million cases expected by 2030, diabetes represents a substantial burden to the overall healthcare system. 1
