ArticleMolecular therapy. Methods & clinical development2014
Development of an inducible caspase-9 safety switch for pluripotent stem cell-based therapies.
Article in Molecular therapy. Methods & clinical development, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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The trial behind it
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Who cites it
45 citing papers in PubMed, 82 citations in OpenAlex.
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- Using the iCasp9 suicide strategy to control the growth and function of genome-edited B cells with redirected antigen specificity.Molecular therapy. Oncology · 2025Article
- Teratoma-free cartilage regeneration using p21-/- iPSCs engineered with iCasp9.Stem cells translational medicine · 2025Article
- Apoptosis-induced nuclear expulsion in tumor cells drives S100a4-mediated metastatic outgrowth through the RAGE pathway.Nature cancer · 2023Article
- Cell-specific regulation of gene expression using splicing-dependent frameshifting.Nature communications · 2022Article
- Inducible caspase-9 suicide gene under control of endogenous oct4 to safeguard mouse and human pluripotent stem cell therapy.Molecular therapy. Methods & clinical development · 2022Article
- Robust In Vitro and In Vivo Immunosuppressive and Anti-inflammatory Properties of Inducible Caspase-9-mediated Apoptotic Mesenchymal Stromal/Stem Cell.Stem cells translational medicine · 2022Article
- Review
- Cell-to-cell variability in inducible Caspase9-mediated cell death.Cell death & disease · 2022Article
- Efficient Genetic Safety Switches for Future Application of iPSC-Derived Cell Transplants.Journal of personalized medicine · 2021Article
- Improved safety of induced pluripotent stem cell-derived antigen-presenting cell-based cancer immunotherapy.Molecular therapy. Methods & clinical development · 2021Article
- Industrializing engineered autologous T cells as medicines for solid tumours.Nature reviews. Drug discovery · 2021Review
- Novel cell sources for bone regeneration.MedComm · 2021Review
- Caspase-9: A Multimodal Therapeutic Target With Diverse Cellular Expression in Human Disease.Frontiers in pharmacology · 2021Review
- Metabolic engineering generates a transgene-free safety switch for cell therapy.Nature biotechnology · 2020Article
- Transient Support from Fibroblasts is Sufficient to Drive Functional Vascularization in Engineered Tissues.Advanced functional materials · 2020Article
- A Preview of Selected Articles.Stem cells translational medicine · 2020Review
- Precision installation of a highly efficient suicide gene safety switch in human induced pluripotent stem cells.Stem cells translational medicine · 2020Article
- CRISPR/Cas9-mediated introduction of the sodium/iodide symporter gene enables noninvasive in vivo tracking of induced pluripotent stem cell-derived cardiomyocytes.Stem cells translational medicine · 2020Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Induced pluripotent stem cell (iPSC) therapies offer a promising path for patient-specific regenerative medicine. However, tumor formation from residual undifferentiated iPSC or transformation of iPSC or their derivatives is a risk. Inclusion of a suicide gene is one approach to risk mitigation. We introduced a dimerizable-"inducible caspase-9" (iCasp9) suicide gene into mouse iPSC (miPSC) and rhesus iPSC (RhiPSC) via a lentivirus, driving expression from either a cytomegalovirus (CMV), elongation factor-1 α (EF1α) or pluripotency-specific EOS-C(3+) promoter. Exposure of the iPSC to the synthetic chemical dimerizer, AP1903, in vitro induced effective apoptosis in EF1α-iCasp9-expressing (EF1α)-iPSC, with less effective killing of EOS-C(3+)-iPSC and CMV-iPSC, proportional to transgene expression in these cells. AP1903 treatment of EF1α-iCasp9 miPSC in vitro delayed or prevented teratomas. AP1903 administration following subcutaneous or intravenous delivery of EF1α-iPSC resulted in delayed teratoma progression but did not ablate tumors. EF1α-iCasp9 expression was downregulated during in vitro and in vivo differentiation due to DNA methylation at CpG islands within the promoter, and methylation, and thus decreased expression, could be reversed by 5-azacytidine treatment. The level and stability of suicide gene expression will be important for the development of suicide gene strategies in iPSC regenerative medicine.
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.