ArticleStem cell research2015
Vpx mediated degradation of SAMHD1 has only a very limited effect on lentiviral transduction rate in ex vivo cultured HSPCs.
Article in Stem cell research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
8 citing papers in PubMed, 12 citations in OpenAlex.
- Enhancing prime editing in hematopoietic stem and progenitor cells by modulating nucleotide metabolism.Nature biotechnology · 2025Article
- Removal of innate immune barriers allows efficient transduction of quiescent human hematopoietic stem cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Review
- Antiviral immunity and nucleic acid sensing in haematopoietic stem cell gene engineering.Gene therapy · 2021Review
- Viral protein X unlocks the nuclear pore complex through a human Nup153-dependent pathway to promote nuclear translocation of the lentiviral genome.Molecular biology of the cell · 2020Article
- Human Dendritic Cell Subsets, Ontogeny, and Impact on HIV Infection.Frontiers in immunology · 2019Review
- The role of SAMHD1 expression and its relation to HIV-2 (Vpx) gene production.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2018Review
- Targeting SAMHD1 with the Vpx protein to improve cytarabine therapy for hematological malignancies.Nature medicine · 2017Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Understanding how to achieve efficient transduction of hematopoietic stem and progenitor cells (HSPCs), while preserving their long-term ability to self-reproduce, is key for applying lentiviral-based gene engineering methods. SAMHD1 is an HIV-1 restriction factor in myeloid and resting CD4+ T cells that interferes with reverse transcription by decreasing the nucleotide pools or by its RNase activity. Here we show that SAMHD1 is expressed at high levels in HSPCs cultured in a medium enriched with cytokines. Thus, we hypothesized that degrading SAMHD1 in HSPCs would result in more efficient lentiviral transduction rates. We used viral like particles (VLPs) containing Vpx, shRNA against SAMHD1, or provided an excess of dNTPs or dNs to study this question. Regardless of the method applied, we saw no increase in the lentiviral transduction rate. The result was different when we used viruses (HR-GFP-Vpx+) which carry Vpx and encode GFP. These viruses allow assessment of the effects of Vpx specifically in the transduced cells. Using HR-GFP-Vpx+ viruses, we observed a modest but significant increase in the transduction efficiency. These data suggest that SAMHD1 has some limited efficacy in blocking reverse transcription but the major barrier for efficient lentiviral transduction occurs before reverse transcription.
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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.