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

项目摘要 体内重编程具有促进高度有希望的和翻译的基因的开发的潜力。 个性化的细胞疗法，用于各种各样的条件。然而，目前的重编程方法， 面临着重大的实际和转化障碍，包括严重依赖病毒转染，以及高度的 随机性质，这通常导致低效和/或不可预测的重编程结果。我们开发 一种新的基于纳米技术的方法，通过实现确定性转导来克服这些障碍， 将因子重编程到组织中，具有单细胞分辨率，而不需要病毒载体。组织 纳米转染（TNT）促进体内非常快速和有效的直接细胞重编程。等 平台技术可以适用于几乎任何重编程模型，其非侵入性和非侵入性， 病毒性质使其成为用于高度复杂疾病系统如糖尿病的理想候选物。这 应用将集中于开发TNT驱动的策略，以实现糖尿病的范式转变细胞疗法， 肥胖症和其它代谢紊乱;通过“再利用”皮肤的部分以达到治疗目的（例如， 感测葡萄糖并相应地释放胰岛素）。因此，本文提出的工作具有根本的创新性 也可能是变革性的

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.