ArticleProceedings of the National Academy of Sciences of the United States of America1998
Consistent, persistent expression from modified retroviral vectors in murine hematopoietic stem cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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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.
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Who cites it
35 citing papers in PubMed.
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- Tagged IDS causes efficient and engraftment-independent prevention of brain pathology during lentiviral gene therapy for Mucopolysaccharidosis type II.Molecular therapy. Methods & clinical development · 2023Article
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- Promoter usage regulating the surface density of CAR molecules may modulate the kinetics of CAR-T cellsMolecular therapy. Methods & clinical development · 2021Article
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- Aberrant Clonal Hematopoiesis following Lentiviral Vector Transduction of HSPCs in a Rhesus Macaque.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- NOTCH1 promotes T cell leukemia-initiating activity by RUNX-mediated regulation of PKC-θ and reactive oxygen species.Nature medicine · 2012Article
- Kruppel-like factor 7 overexpression suppresses hematopoietic stem and progenitor cell function.Blood · 2012Article
- Correction of murine Rag2 severe combined immunodeficiency by lentiviral gene therapy using a codon-optimized RAG2 therapeutic transgene.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Article
- Paucity of HIV DNA methylation in latently infected, resting CD4+ T cells from infected individuals receiving antiretroviral therapy.Journal of virology · 2012Article
- In vivo, in vitro, and in silico analysis of methylation of the HIV-1 provirus.Methods (San Diego, Calif.) · 2011Review
- Serial bone marrow transplantation reveals in vivo expression of the pCLPG retroviral vector.Virology journal · 2010Article
- In vivo stable transduction of humanized liver tissue in chimeric mice via high-capacity adenovirus-lentivirus hybrid vector.Human gene therapy · 2010Article
- Retroviral vector integration in post-transplant hematopoiesis in mice conditioned with either submyeloablative or ablative irradiation.Gene therapy · 2009Article
- CpG methylation controls reactivation of HIV from latency.PLoS pathogens · 2009Article
- Lentiviral-transduced human mesenchymal stem cells persistently express therapeutic levels of enzyme in a xenotransplantation model of human disease.Stem cells (Dayton, Ohio) · 2008Article
- The woodchuck hepatitis virus post-transcriptional regulatory element reduces readthrough transcription from retroviral vectors.Gene therapy · 2007Article
- Gene therapy for severe combined immunodeficiency: are we there yet?The Journal of clinical investigation · 2007Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Retroviral vectors based on the Moloney murine leukemia virus (MoMuLV) have shown inconsistent levels and duration of expression as well as a propensity for the acquisition of de novo methylation in vivo. MoMuLV-based vectors are known to contain sequences that are capable of suppressing or preventing expression from the long terminal repeat. Previously, we constructed a series of modified retroviral vectors and showed that they function significantly better than MoMuLV-based vectors in vitro. To test the efficacy of the modified vectors in hematopoietic stem cells in vivo, we examined gene expression and proviral methylation in differentiated hematopoietic colonies formed in the spleens of mice after serial transplantation with transduced bone marrow (2 degreesCFU-S). We found a significant increase in the frequency of expression with our modified vectors (>90% expression in vector DNA containing 2 degreesCFU-S) over the frequency observed with the standard MoMuLV-based vector (28% expression in vector containing 2 degreesCFU-S). Expression from the modified vectors was highly consistent, with expression in >50% of the vector-containing 2 degreesCFU-S from all 20 transplant recipients analyzed, whereas expression from the standard MoMuLV-based vector was inconsistent, with expression in 0-10% of the vector containing 2 degreesCFU-S from 8 recipients and expression in >50% of the vector-containing 2 degreesCFU-S from 4 other recipients. In addition, we established that the modified vectors had a lower level of DNA methylation than the control vector. These findings represent significant advances in the development and evaluation of effective retroviral vectors for application in vivo.
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