I-Corps: Identifying mutational failure modes of cells

University Of Texas At Austin, Austin TX

Investigators

Abstract

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.