I-Corps: Translation Potential of Rapid In-situ Forming Gel for Local Gene Delivery

I-Corps项目更广泛的影响是基于治疗递送平台的开发，该平台能够将基因疗法局部释放到病变组织。这项技术非常适合于影响粘膜组织的疾病，如眼睛、鼻子、胃肠道和女性生殖道。基因疗法有望减缓这些组织的进展，并有可能治愈影响这些组织的各种疾病。通过最大限度地减少与健康组织的接触，该技术可以提高患者的安全性，并减少管理治疗相关并发症通常所需的医疗保健资源的压力。这个I-Corps项目利用体验式学习和对行业生态系统的第一手调查来评估该技术的翻译潜力。该解决方案是基于生物材料系统的开发，该系统可以以液体形式给药，并且在与目标组织接触后，迅速转化为能够粘附湿粘膜组织的水凝胶。由于基因疗法的效力及其在治疗多种疾病方面的效用，这种水凝胶递送系统将被用作将基因治疗递送到患病部位的治疗仓库。与传统的药物和基因疗法相比，这项创新有几个优势：局部递送避免了与血液中存在的蛋白质和酶的相互作用，而静脉注射时，蛋白质和酶会使基因疗法无效；将治疗有效载荷直接递送到受影响的组织，最大限度地减少了全身暴露和相关副作用，降低了并发症的风险。基因治疗本身是一种有吸引力的治疗方式，因为多个疾病修饰靶点可以同时处理，从而更有效地控制疾病。与传统的小分子（如类固醇和抗生素）和生物（如单克隆抗体）药物相比，基因治疗还可以显著降低患者一生中给药的频率。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact of this I-Corps project is based on the development of a therapeutic delivery platform that is capable of releasing gene therapies locally to diseased tissues. This technology is well-suited for diseases that affect mucosal tissues such as the eyes, nose, and gastrointestinal and female reproductive tracts. Gene therapies hold promise in slowing the progression and potentially curing a wide range of diseases affecting these tissues. By minimizing exposure to healthy tissues, this technology can improve patient safety and reduce the strain on healthcare resources that are often required to manage treatment-related complications. This I-Corps project utilizes experiential learning coupled with a first-hand investigation of the industry ecosystem to assess the translation potential of the technology. The solution is based on the development of a biomaterial system which can be administered in a liquid form and, upon contact on the target tissue, rapidly transforms into a hydrogel capable of adhering to wet mucosal tissues. Owing to the potency of gene therapies and their utility in the treatment of a wide range of diseases, this hydrogel delivery system will be used as a therapeutic depot to deliver gene therapies to the diseased site. This innovation offers several advantages over conventional drug and gene therapies: local delivery avoids interactions with proteins and enzymes present in the blood stream that can render gene therapies ineffective when delivered intravenously and delivering the therapeutic payload directly to the affected tissue minimizes systemic exposure and associated side effects, reducing the risk of complications. Gene therapy itself is an attractive therapeutic modality as multiple disease-modifying targets can be addressed simultaneously for more effective disease management. Gene therapy can also significantly lower the frequency of drug administrations over a patient’s lifetime compared to conventional small molecule (e.g. steroids and antibiotics) and biologic (e.g. monoclonal antibodies) drugs.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.