ArticleNature biotechnology2020
Metabolic engineering generates a transgene-free safety switch for cell therapy.
Article in Nature biotechnology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 52 citations in OpenAlex.
- Genetically engineered hypoimmunogenic iPSCs: Strategies and considerations for clinical applications.Regenerative therapy · 2026Review
- Editing around the target: epitope engineering to protect stem cell grafts.Blood advances · 2026Review
- Global research trends and hotspots of plant physiologically active substances: quantitative visualization analysis based on CiteSpace.Plant biology (Stuttgart, Germany) · 2026Article
- Lentiviral rescue of UMPS auxotrophy enables drug-free selection and stable vector expression.Molecular therapy. Advances · 2026Article
- Gene Editing of Pluripotent Stem Cell-Derived Hepatic Cells for Liver Disease Modeling and Therapeutic Development.Biomolecules & therapeutics · 2026Review
- Non-viral intron knock-ins for targeted gene integration into human T cells and for T-cell selection.Nature biomedical engineering · 2025Article
- Novel strategies to manage CAR-T cell toxicity.Nature reviews. Drug discovery · 2025Review
- Precision Reprogramming in CAR-T Cell Therapy: Innovations, Challenges, and Future Directions of Advanced Gene Editing.International journal of biological sciences · 2025Review
- Thymidylate synthase disruption to limit cell proliferation in cell therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Advanced strategies in improving the immunotherapeutic effect of CAR-T cell therapy.Molecular oncology · 2024Review
- Integration of ζ-deficient CARs into the CD3ζ gene conveys potent cytotoxicity in T and NK cells.Blood · 2024Article
- Article
- Enhancing the safety of CAR-T cell therapy: Synthetic genetic switch for spatiotemporal control.Science advances · 2024Review
- Transient inhibition of 53BP1 increases the frequency of targeted integration in human hematopoietic stem and progenitor cells.Nature communications · 2024Article
- Comparing the Benefits and Drawbacks of Stem Cell Therapy Based on the Cell Origin or Manipulation Process: Addressing Immunogenicity.Immune network · 2023Review
- Homology-independent targeted insertion (HITI) enables guided CAR knock-in and efficient clinical scale CAR-T cell manufacturing.Molecular cancer · 2023Article
- Stable expression of large transgenes via the knock-in of an integrase-deficient lentivirus.Nature biomedical engineering · 2023Article
- Tuning CARs: recent advances in modulating chimeric antigen receptor (CAR) T cell activity for improved safety, efficacy, and flexibility.Journal of translational medicine · 2023Review
- Review
- Marker-free co-selection for successive rounds of prime editing in human cells.Nature communications · 2022Article
Corrections and comments
- Commented on by
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Safeguard mechanisms can ameliorate the potential risks associated with cell therapies but currently rely on the introduction of transgenes. This limits their application owing to immunogenicity or transgene silencing. We aimed to create a control mechanism for human cells that is not mediated by a transgene. Using genome editing methods, we disrupt uridine monophosphate synthetase (UMPS) in the pyrimidine de novo synthesis pathway in cell lines, pluripotent cells and primary human T cells. We show that this makes proliferation dependent on external uridine and enables us to control cell growth by modulating the uridine supply, both in vitro and in vivo after transplantation in xenograft models. Additionally, disrupting this pathway creates resistance to 5-fluoroorotic acid, which enables positive selection of UMPS-knockout cells. We envision that this approach will add an additional level of safety to cell therapies and therefore enable the development of approaches with higher risks, especially those that are intended for limited treatment durations.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.