ArticleStem cells translational medicine2020
Precision installation of a highly efficient suicide gene safety switch in human induced pluripotent stem cells.
Article in Stem cells translational medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 57 citations in OpenAlex.
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- Enhanced disc regeneration through CRISPR/Cas9-mediated SOX9 and TGFβ1 coexpression in tonsil-derived mesenchymal stromal cells.Stem cell research & therapy · 2025Article
- Neural xenografts contribute to long-term recovery in stroke via molecular graft-host crosstalk.Nature communications · 2025Article
- Biological tendon regeneration, are we almost there or is it still a stretch?Regenerative medicine · 2025Article
- Engineering Innate Immunity: Recent Advances and Future Directions for CAR-NK and CAR-Macrophage Therapies in Solid Tumors.Cancers · 2025Review
- Elimination of tumorigenic pluripotent stem cells from their differentiated cell therapy products: An important step toward ensuring safe cell therapy.Stem cell reports · 2025Review
- Induced pluripotent stem cell-derived mesenchymal stem cells for modeling and treating metabolic associated fatty liver disease and metabolic associated steatohepatitis: Challenges and opportunities.World journal of stem cells · 2025Review
- From stem cells to pancreatic β-cells: strategies, applications, and potential treatments for diabetes.Molecular and cellular biochemistry · 2025Review
- Unlocking the therapeutic potential: odyssey of induced pluripotent stem cells in precision cell therapies.International journal of surgery (London, England) · 2024Review
- Regulation of CAR transgene expression to design semiautonomous CAR-T.Molecular therapy. Oncology · 2024Review
- Enhancing clinical safety in bioengineered-root regeneration: The use of animal component-free medium.Heliyon · 2024Article
- Engineering the next generation of theranostic biomaterials with synthetic biology.Bioactive materials · 2024Review
- Advances and challenges in gene therapy strategies for pediatric cancer: a comprehensive update.Frontiers in molecular biosciences · 2024Review
- Challenges of CRISPR/Cas-Based Cell Therapy for Type 1 Diabetes: How Not to Engineer a "Trojan Horse".International journal of molecular sciences · 2023Review
- A mutant methionyl-tRNA synthetase-based toolkit to assess induced-mesenchymal stromal cell secretome in mixed-culture disease models.Stem cell research & therapy · 2023Article
- Clinical Potential of Cellular Material Sources in the Generation of iPSC-Based Products for the Regeneration of Articular Cartilage.International journal of molecular sciences · 2023Review
- A Mutant Methionyl-tRNA Synthetase-Based toolkit to assess induced-Mesenchymal Stromal Cell secretome in mixed-culture disease models.Research square · 2023Article
- Genome editing HLA alleles for a pilot immunocompatible hESC line in a Chinese hESC bank for cell therapies.Cell proliferation · 2023Article
- Building Blocks of Artificial CRISPR-Based Systems beyond Nucleases.International journal of molecular sciences · 2022Review
- Targeted biallelic integration of an inducible Caspase 9 suicide gene in iPSCs for safer therapies.Molecular therapy. Methods & clinical development · 2022Article
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human pluripotent stem cells, including induced pluripotent stem cells (iPSCs) and embryonic stem cells, hold great promise for cell-based therapies, but safety concerns that complicate consideration for routine clinical use remain. Installing a "safety switch" based on the inducible caspase-9 (iCASP9) suicide gene system should offer added control over undesirable cell replication or activity. Previous studies utilized lentiviral vectors to integrate the iCASP9 system into T cells and iPSCs. This method results in random genomic insertion of the suicide switch and inefficient killing of the cells after the switch is "turned on" with a small molecule (eg, AP1903). To improve the safety and efficiency of the iCASP9 system for use in iPSC-based therapy, we precisely installed the system into a genomic safe harbor, the AAVS1 locus in the PPP1R12C gene. We then evaluated the efficiencies of different promoters to drive iCASP9 expression in human iPSCs. We report that the commonly used EF1α promoter is silenced in iPSCs, and that the endogenous promoter of the PPP1R12C gene is not strong enough to drive high levels of iCASP9 expression. However, the CAG promoter induces strong and stable iCASP9 expression in iPSCs, and activation of this system with AP1903 leads to rapid killing and complete elimination of iPSCs and their derivatives, including MSCs and chondrocytes, in vitro. Furthermore, iPSC-derived teratomas shrank dramatically or were completely eliminated after administration of AP1903 in mice. Our data suggest significant improvements on existing iCASP9 suicide switch technologies and may serve as a guide to other groups seeking to improve the safety of stem cell-based therapies.
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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.