ArticleMolecular therapy : the journal of the American Society of Gene Therapy2006
Stable gammaretroviral vector expression during embryonic stem cell-derived in vitro hematopoietic development.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 17 citations in OpenAlex.
- Detailed comparison of retroviral vectors and promoter configurations for stable and high transgene expression in human induced pluripotent stem cells.Gene therapy · 2017Article
- Optimization of methods for the genetic modification of human T cells.Immunology and cell biology · 2015Article
- The use of chromatin insulators to improve the expression and safety of integrating gene transfer vectors.Human gene therapy · 2011Review
- Strategies to insulate lentiviral vector-expressed transgenes.Methods in molecular biology (Clifton, N.J.) · 2010Article
- Development of gene therapy: potential in severe combined immunodeficiency due to adenosine deaminase deficiency.Stem cells and cloning : advances and applications · 2009Review
- Article
- Genomic and functional assays demonstrate reduced gammaretroviral vector genotoxicity associated with use of the cHS4 chromatin insulator.Molecular therapy : the journal of the American Society of Gene Therapy · 2009Article
- Combinatorial incorporation of enhancer-blocking components of the chicken beta-globin 5'HS4 and human T-cell receptor alpha/delta BEAD-1 insulators in self-inactivating retroviral vectors reduces their genotoxic potential.Stem cells (Dayton, Ohio) · 2008Article
- Reducing the genotoxic potential of retroviral vectors.Methods in molecular biology (Clifton, N.J.) · 2008Article
- Progress and prospects: gene transfer into embryonic stem cells.Gene therapy · 2006Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Unlike conventional gammaretroviral vectors, the murine stem cell virus (MSCV) can efficiently express transgenes in undifferentiated embryonic stem cells (ESCs). However, a dramatic extinction of expression is observed when ESCs are subjected to in vitro hematopoietic differentiation. Here we report the construction of a self-inactivating vector from MSCV, MSinSB, which transmits an intron embedded within the internal transgene cassette to transduced cells. The internal transgene transcriptional unit in MSinSB comprises the composite cytomegalovirus immediate early enhancer-chicken beta-actin promoter and associated 5' splice site positioned upstream of the natural 3' splice site of the gammaretroviral envelope gene, and is configured such that the transgene translational initiation sequence is coincident with the envelope ATG. MSinSB could be produced at titers approaching 10(6) transducing units/ml and directed higher levels of transgene expression in ESCs than a splicing-optimized MSCV-derived vector, MSGV1. Moreover, when transduced ESCs were differentiated into hematopoietic cells in vitro, MSinSB remained transcriptionally active in greater than 90% of the cells, whereas MSGV1 expression was almost completely shut off. Persistent high-level expression of the MSinSB gammaretroviral vector was also demonstrated in murine bone marrow transplant recipients and following in vitro myelomonocytic differentiation of human CD34(+) cord blood stem/progenitor cells.
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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.