ArticleMolecular therapy : the journal of the American Society of Gene Therapy2012
Thymidine kinase suicide gene-mediated ganciclovir ablation of autologous gene-modified rhesus hematopoiesis.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Ganciclovir as a potential treatment for glioma: a systematic review and meta-analysis.Journal of neuro-oncology · 2023Pooled it
- Comparison of busulfan and total body irradiation conditioning on hematopoietic clonal dynamics following lentiviral gene transfer in rhesus macaques.Molecular therapy. Methods & clinical development · 2023Article
- Versatile cell ablation tools and their applications to study loss of cell functions.Cellular and molecular life sciences : CMLS · 2019Review
- A Cetuximab-Mediated Suicide System in Chimeric Antigen Receptor-Modified Hematopoietic Stem Cells for Cancer Therapy.Human gene therapy · 2019Article
- Switching on the green light for chimeric antigen receptor T-cell therapy.Clinical & translational immunology · 2019Review
- Pre-clinical development of gene modification of haematopoietic stem cells with chimeric antigen receptors for cancer immunotherapy.Human vaccines & immunotherapeutics · 2017Article
- Genetically engineered suicide gene in mesenchymal stem cells using a Tet-On system for anaplastic thyroid cancer.PloS one · 2017Article
- Retroviral vectors and transposons for stable gene therapy: advances, current challenges and perspectives.Journal of translational medicine · 2016Review
- Conditional Cytotoxic Anti-HIV Gene Therapy for Selectable Cell Modification.Human gene therapy · 2016Article
- Regulated apoptosis of genetically modified hematopoietic stem and progenitor cells via an inducible caspase-9 suicide gene in rhesus macaques.Stem cells (Dayton, Ohio) · 2015Article
- Vector modifications to eliminate transposase expression following piggyBac-mediated transgenesis.Scientific reports · 2014Article
- HSV-sr39TK positron emission tomography and suicide gene elimination of human hematopoietic stem cells and their progeny in humanized mice.Cancer research · 2014Article
- New viruses for cancer therapy: meeting clinical needs.Nature reviews. Microbiology · 2014Review
- Gene-modified hematopoietic stem cells for cancer immunotherapy.Human vaccines & immunotherapeutics · 2014Article
- Development of an inducible caspase-9 safety switch for pluripotent stem cell-based therapies.Molecular therapy. Methods & clinical development · 2014Article
- Myeloprotection by cytidine deaminase gene transfer in antileukemic therapy.Neoplasia (New York, N.Y.) · 2013Review
- Conditional negative selection of gene-modified hematopoietic stem cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Article
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8 authors at 4 institutions in 2 countries.
Funding
Abstract
Despite the genotoxic complications encountered in clinical gene therapy trials for primary immunodeficiency diseases targeting hematopoietic cells with integrating vectors; this strategy holds promise for the cure of several monogenic blood, metabolic and neurodegenerative diseases. In this study, we asked whether the inclusion of a suicide gene in a standard retrovirus vector would allow elimination of vector-containing stem and progenitor cells and their progeny in vivo following transplantation, using our rhesus macaque transplantation model. Following stable engraftment with autologous CD34(+) cells transduced with a retrovirus vector encoding a highly sensitive modified Herpes simplex virus thymidine kinase SR39, the administration of the antiviral prodrug ganciclovir (GCV) was effective in completely eliminating vector-containing cells in all hematopoietic lineages in vivo. The sustained absence of vector-containing cells over time, without additional GCV administration, suggests that the ablation of TkSR39 GCV-sensitive cells occurred in the most primitive hematopoietic long-term repopulating stem or progenitor cell compartment. These results are a proof-of-concept that the inclusion of a suicide gene in integrating vectors, in addition to a therapeutic gene, can provide a mechanism for later elimination of vector-containing cells, thereby increasing the safety of gene transfer.
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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.