10170622Reversing Diabetes Through In Vivo Pancreatic Cell Reprogramming: An Engineering Biology StrategyClosedFast Start ResponseInnovate UKPNAS Therapeutics is developing **InsuGen**, a groundbreaking platform that combines advanced pancreatic cell reprogramming with proprietary engineered hydrogel delivery technology to address Type 1 diabetes at its root cause. Unlike conventional treatments that merely manage symptoms, our innovation targets the autoimmune destruction of beta cells by both protecting existing cells and creating new insulin sources through cellular reprogramming. Our dual technology approach offers three key innovations: * **Alpha-to-Beta Cell Conversion:** Our proprietary synthetic transcription factor combinations (PDX1, NGN3, MAFA) enable efficient reprogramming of abundant pancreatic alpha cells into insulin-producing beta cells, creating new insulin sources that potentially bypass established autoimmune recognition patterns. * **Advanced Genetic Cargo:** We utilise a strategic combination of modified mRNA for immediate but transient expression and minicircle cDNA for sustained reprogramming effects, optimized with engineered UTRs and minimal bacterial sequences to enhance efficiency while reducing immunogenicity. * **Protective Hydrogel Microenvironment:** Our rapid self-assembling hydrogel (complete in just 5 minutes) forms immune-privileged spaces around both remaining beta cells and newly reprogrammed cells, while providing sequential delivery of reprogramming factors in developmentally optimal order. * **Precision Delivery System:** Our technology ensures targeted delivery of therapeutic cargos specifically to pancreatic tissue through minimally invasive local injection, maximizing efficacy while minimizing off-target effects and systemic exposure. This project will advance our technology from TRL2 to TRL3 by optimizing our synthetic biology reprogramming protocols and demonstrating proof-of-concept in relevant cellular models. The successful development of InsuGen could transform Type 1 diabetes treatment by potentially inducing partial remission, reducing insulin dependence, and improving quality of life for millions of patients worldwide.