SBIR Phase I: Development of an Adjustable Gene Therapy Platform Technology

这个小企业创新研究（SBIR）第一阶段项目的更广泛/商业影响包括开发一个基因治疗平台，该平台将允许在罕见疾病以外的领域使用基因治疗，解决糖尿病，骨关节炎和自身免疫性疾病等大量未满足的临床需求。该项目还将大大降低基因疗法和基于蛋白质的疗法的成本。最后，拟议的平台技术的开发将使医疗产品的注射频率降低，产生潜在的更优化的治疗方案，并防止与错过剂量或治疗过量相关的并发症。该技术的社会和商业影响是显著的，因为所提出的技术可以极大地扩展基因治疗的潜力，同时用更低成本的替代品取代其他基于生物的疗法。该技术具有重要的商业价值，但同时能够大大降低与当前治疗方法相关的社会医疗成本。该项目开发了一种剂量可调的基因治疗机制，可用于在初始给药后上调或下调基因治疗剂量。尽管最近的进展和监管批准，基因治疗仍然有限，由于其固有的缺点，在剂量调整-一旦基因治疗剂量的管理，它不能增加或减少二次干预。另一方面，许多治疗需要在数周或数月的时间内调整最初处方的剂量，以优化疗效和副作用。该项目旨在开发和表征第一种完全可调节的基因疗法，能够进行可预测的治疗后剂量调整。为了实现这一目标，作为该项目的一部分，将解决一些技术障碍，包括将遗传物质非病毒递送到人类细胞，以可预测和可测量的方式控制基因表达的能力，以及确保任何可调节性对患者器官，组织，该奖项反映了NSF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进行评估，被认为值得支持的搜索.

The broader/commercial impacts of this Small Business Innovation Research (SBIR) Phase I project include the development of a gene therapy platform that will allow the use of genetic therapeutics in areas beyond rare diseases, tackling large unmet clinical needs such as diabetes, osteoarthritis, and autoimmune diseases. The project will also enable significant reductions in the costs of gene therapies and protein-based therapeutics. Finally, the development of the proposed platform technology will enable the production of medical treatments that are injected less frequently, produce a potentially more optimal treatment profile, and prevent complications related to missed doses or therapeutic overdose. The societal and commercial impacts of this technology are significant, as the proposed technology could greatly expand the potential of gene therapy, while replacing other biologic-based therapies with a lower cost alternative. The technology has significant commercial value but is, at the same time, able to greatly reduce societal medical costs associated with current treatment approaches.This project develops a dose-adjustable gene therapy mechanism that can be used to up- or down-regulate a gene therapy dose, following initial administration. Despite recent advances and regulatory approvals, gene therapy remains limited due to its inherent shortcomings in dose adjustment – once a gene therapy dose is administered, it cannot be increased or decreased by secondary intervention. On the other hand, many therapeutics require adjustment of the initially prescribed dose over a period of weeks or months to optimize the efficacy and side-effects profile. This project aims to develop and characterize the first, fully adjustable gene therapy, capable of predictable post-treatment dose adjustment. To accomplish this, a number of technological hurdles will be addressed as part of the project including non-viral delivery of genetic material to human cells, the ability to control the gene expression in a predictable and measurable manner, and the assurance that any adjustability is safe to the patient organs, tissues, and cells that neighbor the treatment area.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.