I-Corps: Genetically Enhanced Red Blood Cell Technology

该I-Corps项目的更广泛影响/商业潜力是开发一种更安全，可靠供应和具有成本效益的红细胞产品，可能有潜力解决全球血液短缺问题，缓解当前献血者血液供应链的许多后勤挑战，并降低输血医学风险。在美国26亿美元的红血市场中，血库主管在维持日常血液供应、管理全面和密集的检测团队、实施新检测以及管理医院内分配方面面临着深刻的物流挑战。这项技术将通过基因工程人类干细胞来创造，以促进它们在实验室环境中分化为成熟的红细胞。这将允许理论上无限供应的红细胞，独立于人类供体，可以制成任何血型并按需生产。这项拟议中的技术可能会通过确保红血供应和降低与输血相关的风险来影响公众健康。这也会影响与红细胞相关的科学研究。这个I-Corps项目探索了一种可扩展的方法的翻译，用于通过使用新型基因工程技术大规模生产增强的红细胞产品。体外将干细胞分化为红细胞的过程已经很好地建立，但已经显示出具有限制翻译的几个问题，包括生产和细胞培养扩增的成本。对干细胞基因组的特定修饰和优化的制造条件可能有助于促进离体红细胞合成的更广泛传播。该项目将推进特定目标的基因工程技术的发展，以实现更高的细胞生产率和诱导可控的细胞状态。该奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

The broader impact/commercial potential of this I-Corps project is the development of a safer, reliably supplied, and cost-effective red blood cell product that may have the potential to address global blood scarcities, relieve many of the logistical challenges of the current donor blood supply chain, and decrease risk in transfusion medicine. Blood bank directors in the United States’ $2.6 billion red blood market face deep logistical challenges in maintaining the daily blood supply, managing comprehensive and intensive testing regiments, implementing new tests, and managing intra-hospital distribution. This technology will be created by genetically engineering human stem cells to promote their differentiation into mature red blood cells, within a laboratory environment. This would allow a theoretically limitless supply of red blood cells, independent of human donors, that could be made to be any blood type and created on demand. The proposed technology may impact public health by ensuring supply of red blood and reducing the risks associated with transfusions. This can also impact scientific research related to red blood cells. This I-Corps project explores translation of a scalable method for mass-producing an enhanced red blood cell product created through the use of novel genetic engineering techniques. The process of differentiating stem cells into erythrocytes in vitro is well established but has been shown to have several issues limiting translation, including the cost of production and cell culture expansion. Specific modifications to the stem cell genome and optimized manufacturing conditions may help promote wider dissemination of ex vivo red blood cell synthesis. This project will advance the development of specifically targeted genetic engineering techniques to enable higher cellular production rates and to induce controllable cellular states.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.