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Adv. Sci., Aug 06 2024, | https://doi.org/10.1002/advs.202405593
SiMPl-GS: Advancing Cell Line Development via Synthetic Selection Marker for Next-Generation Biopharmaceutical Production
Chansik Yoon 1, Eun-Ji Lee 2 3, Dongil Kim 1, Siyun Joung 1, Yujin Kim 1, Heungchae Jung 3 4, Yeon-Gu Kim 2 3, Gyun Min Lee 1 *
1Department of Biological Sciences, KAIST, Daejeon, 34141, Republic of Korea.
2Biotherapeutics Translational Research Center, KRIBB, Daejeon, 34113, Republic of Korea.
3Department of Bioprocess Engineering, KRIBB School of Biotechnology, UST, Daejeon, 34141, Republic of Korea.
4BIO Center, Daejeon Technopark, Daejeon, 34054, Republic of Korea.
*Corresponding author: correspondence to Gyun Min Lee
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 produce high levels of therapeutic proteins. Harnessing orthogonal split intein pairs further enables the selection of four plasmids with a single selection, streamlining multispecific antibody-producing CLD. Taken together, SiMPl-GS is a simple yet effective means to expedite CLD for therapeutic protein production.
논문정보
- Research article
- 2024년 08월 (BRIC 등록일 2024-08-07)
- 국내 연구진
- 생명과학 > 생물공학
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