Thymidylate synthase disruption to limit cell proliferation in cell therapies.

Journal

Molecular therapy : the journal of the American Society of Gene Therapy
ISSN: 1525-0024
Titre abrégé: Mol Ther
Pays: United States
ID NLM: 100890581

Informations de publication

Date de publication:
12 Jun 2024
Historique:
received: 15 04 2024
revised: 10 06 2024
accepted: 10 06 2024
medline: 13 6 2024
pubmed: 13 6 2024
entrez: 13 6 2024
Statut: aheadofprint

Résumé

Stem and progenitor cells hold great promise for regenerative medicine and gene therapy approaches. However, transplantations of living cells entail 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

Identifiants

DOI: 10.1016/j.ymthe.2024.06.014 PMID: 38867450
pubmed: 38867450
pii: S1525-0016(24)00396-4
doi: 10.1016/j.ymthe.2024.06.014
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024. Published by Elsevier Inc.

Auteurs

Rocio Sartori-Maldonado (R)

Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, 00290, Helsinki, Finland.

Hossam Montaser (H)

Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, 00290, Helsinki, Finland.

Inkeri Soppa (I)

Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, 00290, Helsinki, Finland.

Solja Eurola (S)

Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, 00290, Helsinki, Finland.

Juhana Juutila (J)

Faculty of Biological and Environmental Sciences University of Helsinki, 00790, Helsinki, Finland; Institute of Biotechnology, Helsinki Institute of Life Science, University of Helsinki, 00790, Helsinki, Finland.

Melanie Balaz (M)

Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, 00290, Helsinki, Finland.

Henri Puttonen (H)

Department of Pathology, Helsinki University Hospital, 00290, Helsinki, Finland.

Timo Otonkoski (T)

Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, 00290, Helsinki, Finland; Children's Hospital, University of Helsinki and Helsinki University Hospital, 00290, Helsinki, Finland.

Jonna Saarimäki-Vire (J)

Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, 00290, Helsinki, Finland.

Kirmo Wartiovaara (K)

Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, 00290, Helsinki, Finland; Clinical Genetics, Helsinki University Hospital, 00290, Helsinki, Finland. Electronic address: kirmo.wartiovaara@helsiki.fi.

Classifications MeSH