ArticlePLoS pathogens2018
Differential impact of transplantation on peripheral and tissue-associated viral reservoirs: Implications for HIV gene therapy.
Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 41 citations in OpenAlex.
- Antigen-boosted CD4CAR T cells fail to expand or control viremia in multiple nonhuman primate models of HIV.Blood · 2026Article
- Smac mimetic combined with eCD4-Ig reverses latency without reducing SHIV reservoirs in rhesus macaques.The Journal of clinical investigation · 2026Article
- Engraftment of gene-edited hematopoietic stem cells after antibody-drug conjugate conditioning in nonhuman primates.Blood advances · 2026Article
- High frequency CCR5 editing in human hematopoietic stem progenitor cells protects xenograft mice from HIV infection.Nature communications · 2025Article
- In pursuit of an HIV cure: from stem cell transplants to gene therapies.Frontiers in genome editing · 2025Review
- CD20 CAR T cells safely and reversibly ablate B cell follicles in a non-human primate model of HIV persistence.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Stem cell-derived CAR T cells show greater persistence, trafficking, and viral control compared to ex vivo transduced CAR T cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- In vivo selection of anti-HIV-1 gene-modified human hematopoietic stem/progenitor cells to enhance engraftment and HIV-1 inhibition.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Efficient manufacturing and engraftment ofMolecular therapy. Methods & clinical development · 2023Article
- Advances in HIV therapeutics and cure strategies: findings obtained through non-human primate studies.Journal of neurovirology · 2023Review
- EfficientFrontiers in immunology · 2023Article
- Strategies for enhancing CAR T cell expansion and persistence in HIV infection.Frontiers in immunology · 2023Review
- Intracellular RNase activity dampens zinc finger nuclease-mediated gene editing in hematopoietic stem and progenitor cells.Molecular therapy. Methods & clinical development · 2022Article
- Genome editing in large animal models.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- The Strategies and Challenges of CCR5 Gene Editing in Hematopoietic Stem and Progenitor Cells for the Treatment of HIV.Stem cell reviews and reports · 2021Review
- Generation of HIV-resistant cells with a single-domain antibody: implications for HIV-1 gene therapy.Cellular & molecular immunology · 2021Article
- Article
- Stem cell-derived CAR T cells traffic to HIV reservoirs in macaques.JCI insight · 2021Article
- CRISPR/Cas9 for the treatment of haematological diseases: a journey from bacteria to the bedside.British journal of haematology · 2021Review
- Dual CD4-based CAR T cells with distinct costimulatory domains mitigate HIV pathogenesis in vivo.Nature medicine · 2020Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
Autologous transplantation and engraftment of HIV-resistant cells in sufficient numbers should recapitulate the functional cure of the Berlin Patient, with applicability to a greater number of infected individuals and with a superior safety profile. A robust preclinical model of suppressed HIV infection is critical in order to test such gene therapy-based cure strategies, both alone and in combination with other cure strategies. Here, we present a nonhuman primate (NHP) model of latent infection using simian/human immunodeficiency virus (SHIV) and combination antiretroviral therapy (cART) in pigtail macaques. We demonstrate that transplantation of CCR5 gene-edited hematopoietic stem/progenitor cells (HSPCs) persist in infected and suppressed animals, and that protected cells expand through virus-dependent positive selection. CCR5 gene-edited cells are readily detectable in tissues, namely those closely associated with viral reservoirs such as lymph nodes and gastrointestinal tract. Following autologous transplantation, tissue-associated SHIV DNA and RNA levels in suppressed animals are significantly reduced (p ≤ 0.05), relative to suppressed, untransplanted control animals. In contrast, the size of the peripheral reservoir, measured by QVOA, is variably impacted by transplantation. Our studies demonstrate that CCR5 gene editing is equally feasible in infected and uninfected animals, that edited cells persist, traffic to, and engraft in tissue reservoirs, and that this approach significantly reduces secondary lymphoid tissue viral reservoir size. Our robust NHP model of HIV gene therapy and viral persistence can be immediately applied to the investigation of combinatorial approaches that incorporate anti-HIV gene therapy, immune modulators, therapeutic vaccination, and latency reversing agents.
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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.