SiMPl-GS: Advancing Cell Line Development via Synthetic Selection Marker for Next-Generation Biopharmaceutical Production.

ABSTRACT: Rapid and efficient cell line development (CLD) process is essential to expedite therapeutic protein development. However, the performance of widely used glutamine-based selection systems is limited by low selection efficiency, stringency, and the inability to select multiple genes. Therefore, an AND-gate synthetic selection system is rationally designed using split intein-mediated protein ligation of glutamine synthetase (GS) (SiMPl-GS). Split sites of the GS are selected using a computational approach and validated with GS-knockout Chinese hamster ovary cells for their potential to enable cell survival in a glutamine-free medium. In CLD, SiMPl-GS outperforms the wild-type GS by selectively enriching high producers. Unlike wild-type GS, SiMPl-GS results in cell pools in which most cells p

SUBMITTER: Yoon C 

PROVIDER: S-EPMC11481413 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature