I-Corps: Identifying mutational failure modes of cells

I-Corps项目更广泛的影响/商业潜力是降低成本，增加生物燃料、化学品和治疗药物的多样性，这些生物燃料、化学品和治疗药物可以由工程细胞生产，这些细胞被用作生物制造业的“活工厂”。因为细胞是活的，它们在生长过程中会积累突变。这些突变通常会降低甚至消除细胞制造其设计制造的产品的能力。该项目旨在将诊断在大型生物反应器生产过程中这些细胞中积累的“失败”突变的技术商业化。这种能力将为生物技术公司提供有价值的信息，他们可以利用这些信息来重新设计细胞，以防止突变导致产品产量的损失。因此，它有可能加速许多新的可再生生物制造工艺的进展，从早期的研发测试阶段到经济上可行的大规模商业生产。I-Corps项目的核心技术是通过结合先进的下一代测序和软件工作流程，为生物制造中使用的细胞提供遗传稳定性诊断报告。这一过程可以识别导致细胞群体生产损失的突变，而它们比用标准方法检测到的要少几千倍。在细胞小规模生长时很少发生的突变，在细胞大规模生长时就会成为显性突变。许多这种潜在的未来失效突变可以在一个小型生物反应器中使用这种技术进行分析。通过这种方式，在研发流程的早期全面识别故障突变，这样他们就可以在扩大规模之前重新设计细胞以防止这些问题，从而节省公司开发这些工艺的时间和金钱。该项目探索了一项服务的商业可行性，该服务为生物制造公司提供这些“稳定性报告”，使他们能够更快地克服与突变相关的研究和开发障碍。

The broader impact/commercial potential of this I-Corps project is to lower costs and increase the diversity of biofuels, chemicals, and therapeutics that can be produced by engineered cells that are used as 'living factories' in the biomanufacturing industry. Because cells are alive, they accumulate mutations as they grow. These mutations often reduce or even eliminate a cell's ability to make the product it was designed to manufacture. This project aims to commercialize technology for diagnosing what 'failure' mutations accumulate in these cells during production in large bioreactors. This capability will provide biotech companies with valuable information that they can use to re-engineer cells to prevent mutations from leading to losses of product yield. Thus, it has the potential to speed the progress of many new, renewable biomanufacturing processes from early R&D test stages to economically viable commercial production at scale.This I-Corps project centers on technology that provides diagnostic reports on the genetic stability of cells used in biomanufacturing through a combination of advanced next-generation sequencing and software workflows. This process can identify mutations that lead to a loss of production in a cell population while they are thousands of times rarer than can be detected by standard methods. Mutations that are rare when cells are grown at small scale will become dominant when cells are grown at larger production scales. Many such potential future failure mutations can be profiled in one small bioreactor using this technology. Comprehensively identifying failure mutations earlier in a R&D pipeline in this way such that they can re-engineer cells to prevent these problems before scale-up will save companies developing these processes time and money. This project explores the commercial viability of a service that provides these 'stability reports' to biomanufacturing companies in order to allow them to more rapidly overcome research and development obstacles related to mutations.