ArticlePloS one2013
Deletion of the LTR enhancer/promoter has no impact on the integration profile of MLV vectors in human hematopoietic progenitors.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Regulatory Consideration for the Nonclinical Safety Assessment of Gene Therapies.Human gene therapy · 2022Article
- Improved functionality and potency of next generation BinMLV viral vectors toward safer gene therapy.Molecular therapy. Methods & clinical development · 2021Article
- Immune Reconstitution After Gene Therapy Approaches in Patients With X-Linked Severe Combined Immunodeficiency Disease.Frontiers in immunology · 2020Review
- Disrupting MLV integrase:BET protein interaction biases integration into quiescent chromatin and delays but does not eliminate tumor activation in a MYC/Runx2 mouse model.PLoS pathogens · 2019Article
- Preclinical Development of a Lentiviral Vector for Gene Therapy of X-Linked Severe Combined Immunodeficiency.Molecular therapy. Methods & clinical development · 2018Article
- Engineering Next-Generation BET-Independent MLV Vectors for Safer Gene Therapy.Molecular therapy. Nucleic acids · 2017Article
- Prolonged Integration Site Selection of a Lentiviral Vector in the Genome of Human Keratinocytes.Medical science monitor : international medical journal of experimental and clinical research · 2017Article
- Gene Therapy for X-Linked Severe Combined Immunodeficiency: Where Do We Stand?Human gene therapy · 2016Review
- BET-independent MLV-based Vectors Target Away From Promoters and Regulatory Elements.Molecular therapy. Nucleic acids · 2014Article
- Novel principles of gamma-retroviral insertional transcription activation in murine leukemia virus-induced end-stage tumors.Retrovirology · 2014Article
- Genome-wide analysis of alpharetroviral integration in human hematopoietic stem/progenitor cells.Genes · 2014Article
- Self-inactivating MLV vectors have a reduced genotoxic profile in human epidermal keratinocytes.Gene therapy · 2013Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Moloney murine leukemia virus (MLV)-derived gamma-retroviral vectors integrate preferentially near transcriptional regulatory regions in the human genome, and are associated with a significant risk of insertional gene deregulation. Self-inactivating (SIN) vectors carry a deletion of the U3 enhancer and promoter in the long terminal repeat (LTR), and show reduced genotoxicity in pre-clinical assays. We report a high-definition analysis of the integration preferences of a SIN MLV vector compared to a wild-type-LTR MLV vector in the genome of CD34(+) human hematopoietic stem/progenitor cells (HSPCs). We sequenced 13,011 unique SIN-MLV integration sites and compared them to 32,574 previously generated MLV sites in human HSPCs. The SIN-MLV vector recapitulates the integration pattern observed for MLV, with the characteristic clustering of integrations around enhancer and promoter regions associated to H3K4me3 and H3K4me1 histone modifications, specialized chromatin configurations (presence of the H2A.Z histone variant) and binding of RNA Pol II. SIN-MLV and MLV integration clusters and hot spots overlap in most cases and are generated at a comparable frequency, indicating that the reduced genotoxicity of SIN-MLV vectors in hematopoietic cells is not due to a modified integration profile.
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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.