Thymidylate synthase disruption to limit cell proliferation in cell therapies.

ABSTRACT: Stem and progenitor cells hold great promise for regenerative medicine and gene therapy approaches. However, transplantation of living cells entails a fundamental risk of unwanted growth, potentially exacerbated by CRISPR-Cas9 or other genetic manipulations. Here, we describe a safety system to control cell proliferation while allowing robust and efficient cell manufacture, without any added genetic elements. Inactivating TYMS, a key nucleotide metabolism enzyme, in several cell lines resulted in cells that proliferate only when supplemented with exogenous thymidine. Under supplementation, TYMS^-/--pluripotent stem cells proliferate, produce teratomas, and successfully differentiate into potentially therapeutic cell types such as pancreatic β cells. Our results suggest that suppl

SUBMITTER: Sartori-Maldonado R 

PROVIDER: S-EPMC11405178 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature