I-Corps: High Efficiency Transduction to Improve Manufacture of Cell Therapeutics

这个i-Corps项目的更广泛的影响/商业潜力是改进基因和细胞疗法，这些疗法有可能在包括癌症、血液疾病和遗传病在内的广泛疾病的医疗保健方面做出改变生活的改善。如果成功，该项目可以通过降低生产成本和实现由于现有细胞工程过程的低效率而目前不可行的新疗法来帮助扩大获得这些疗法的人口。该团队将寻求学习新的想法和方法，让参与者和利益相关者参与细胞治疗社区。这包括合同制造组织、临床医生/医生、监管代表、制药公司和患者权益倡导者等。除了细胞和基因疗法外，该团队还将与在基础生物学和药物发现应用中使用基因修饰的研究人员建立联系。如果在所有方面都成功，这个项目有可能帮助发现和提供许多治疗无法治愈的疾病的新疗法。这个i-Corps项目解决了细胞工程过程中的一个低效问题。在细胞疗法中，患者细胞被重新编程为基因序列，以改变细胞行为。这可能包括教导免疫细胞清除癌症，或者重新编程骨髓细胞以产生缺失的凝血因子蛋白来治愈先天性疾病。尽管这些治疗方法显示出巨大的潜力，但许多治疗方法都存在基因转移效率低的问题。在某些情况下，低效率可能会阻止治疗有效。最先进的技术是使用慢病毒将基因导入细胞，通常每个细胞使用20-50个病毒颗粒。然而，已经清楚地表明，很大一部分病毒载体被浪费了，这主要是由于大规模运输的限制。该项目建议提供一种试剂，将细胞转导中使用的慢病毒数量减少10倍，并在最大限度地减少对现有转导方案的干扰的情况下提高转导效率。这一过程使细胞与病毒共同定位，以缩短扩散距离，同时保持温和的含水环境并保留大量细胞培养营养物质。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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/commercial potential of this I-Corps project is to improve gene and cell therapies which hold potential to make life-altering improvements in healthcare for a broad spectrum of diseases, including cancers, blood disorders, and genetic diseases. If successful, this project can help to expand the population that has access to these treatments, both by reducing the cost of production and by enabling new therapies that are currently infeasible due to the low efficiency of existing cell engineering processes. The team will seek to learn new ideas and methodologies for engaging participants and stakeholders in the cell therapy community. This includes contract manufacturing organizations, clinicians/physicians, regulatory representatives, pharmaceutical companies, and patient advocates, among others. In addition to cell and gene therapies, the team will connect with researchers using gene modification in basic biology and drug discovery applications. If successful on all fronts, this project has potential to aid the discovery and delivery of many new therapies for untreatable diseases.This I-Corps project addresses an inefficiency in the cell engineering process. In cell therapies, patient cells are reprogrammed with a genetic sequence to alter the cell behavior. This can involve teaching immune cells to clear cancer, or reprogramming bone marrow cells to produce missing clotting factor proteins to cure congenital disease. Although these treatments have demonstrated tremendous potential, many of the treatments suffer from the low efficiency of gene transfer. In some cases, the low efficiency may prevent the treatment from being effective. The state of the art uses lentivirus to introduce genes into cells, typically using 20-50 viral particles per cell. However, it has been clearly shown that a great portion of the virus vector is wasted, due largely to mass transport limitations. This project proposes to provide a reagent to decrease the quantity of lentivirus used in cell transductions by 10-fold and improve transduction efficiency with minimal disruption of current transduction protocols. This process co-localizes cells with virus to reduce diffusion distances, while maintaining a mild, aqueous environment and retaining a large reservoir of cell culture nutrients.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.