ArticleMolecular therapy. Nucleic acids2016
Escape Mutations, Ganciclovir Resistance, and Teratoma Formation in Human iPSCs Expressing an HSVtk Suicide Gene.
Article in Molecular therapy. Nucleic acids, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 30 citations in OpenAlex.
- Elimination of tumorigenic pluripotent stem cells from their differentiated cell therapy products: An important step toward ensuring safe cell therapy.Stem cell reports · 2025Review
- Recent updates on allogeneic CAR-T cells in hematological malignancies.Cancer cell international · 2024Review
- Developing and characterizing a two-layered safety switch for cell therapies.Cancer biology & therapy · 2023Article
- Pancreatic β-Cell Development and Regeneration.Cold Spring Harbor perspectives in biology · 2022Review
- Strategies to Improve the Safety of iPSC-Derived β Cells for β Cell Replacement in Diabetes.Transplant international : official journal of the European Society for Organ Transplantation · 2022Review
- Efficient Genetic Safety Switches for Future Application of iPSC-Derived Cell Transplants.Journal of personalized medicine · 2021Article
- Human stem cells harboring a suicide gene improve the safety and standardisation of neural transplants in Parkinsonian rats.Nature communications · 2021Article
- Diagnosis and treatment of type 1 diabetes at the dawn of the personalized medicine era.Journal of translational medicine · 2021Review
- Review
- Human Genomic Safe Harbors and the Suicide Gene-Based Safeguard System for iPSC-Based Cell Therapy.Stem cells translational medicine · 2019Article
- A Double Fail-Safe Approach to Prevent Tumorigenesis and Select Pancreatic β Cells from Human Embryonic Stem Cells.Stem cell reports · 2019Article
- Linking a cell-division gene and a suicide gene to define and improve cell therapy safety.Nature · 2018Article
- Multimodality molecular imaging in cardiac regenerative therapy.Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology · 2017Article
- Technical approaches to induce selective cell death of pluripotent stem cells.Cellular and molecular life sciences : CMLS · 2017Review
- Elimination of proliferating cells from CNS grafts using a Ki67 promoter-driven thymidine kinase.Molecular therapy. Methods & clinical development · 2016Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Human pluripotent stem cells (hPSCs) hold great promise for cell therapy. However, a major concern is the risk of tumor formation by residual undifferentiated cells contaminating the hPSC-derived cell product. Suicide genes could safeguard against such adverse events by enabling elimination of cells gone astray, but the efficacy of this approach has not yet been thoroughly tested. Here, we engineered a lentivirally encoded herpes simplex virus thymidine kinase (HSVtk) with expression restricted to undifferentiated hPSCs through regulation by the let7 family of miRNAs. We show that induced pluripotent stem cells (iPSCs) expressing a let7-regulated HSVtk transgene are selectively killed by ganciclovir (GCV), whereas differentiated cells are fully protected. However, in contrast to previous studies, we find that in vivo GCV administration results in longer latency but does not prevent teratoma formation by iPSCs expressing either a constitutive or a let7-regulated HSVtk, without evidence of silencing of the HSVtk. Clonal analyses of iPSCs expressing HSVtk revealed frequent emergence of GCV resistance which, at least in some cases, could be attributed to preexisting inactivating mutations in the HSVtk coding sequence, selected for upon GCV treatment. Our findings have important consequences for the future use of suicide genes in hPSC-based cell therapies.
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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.