ArticleCell stem cell2024
A simultaneous knockout knockin genome editing strategy in HSPCs potently inhibits CCR5- and CXCR4-tropic HIV-1 infection.
Article in Cell stem cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Engineering hematopoietic stem and progenitor cells to generate red blood cells as viral traps against HIV-1.Molecular therapy. Advances · 2026Article
- CCR5 as a Therapeutic Target in HIV Disease: From CRISPR/Cas9 Gene Editing to Maraviroc-Mediated Inhibition.Viruses · 2026Review
- Article
- Engineered hematopoietic stem cells give rise to therapeutic antibody secreting B cells.Research square · 2026Article
- Engraftment Outcome of CRISPR/Cas9-Edited Hematopoietic Stem Cells for Genetic Diseases: A Systematic Review and Meta-Analysis of Preclinical Evidence.Journal of hematology · 2026Article
- CXCR4-tropic HIV-1 infection in an immunocompetent monkey model.Nature communications · 2026Article
- RhCMV expands CCR5+ memory T cells and promotes SIV reservoir seeding in the gut mucosa.JCI insight · 2026Article
- Research progress on HIV-1 structural proteins and antiviral therapies.Frontiers in immunology · 2026Review
- Host restriction factors and p17-Driven inflammaging in HIV-1: From molecular pathogenesis to functional cure.AIMS microbiology · 2026Review
- Circular single stranded DNA potentiates non-viral gene insertion in hematopoietic stem and progenitor cells.Nature communications · 2025Article
- CRISPR/Cas9 for achieving postintervention HIV control.Current opinion in HIV and AIDS · 2025Review
- Multilayered HIV-1 resistance in HSPCs through CCR5 Knockout and B cell secretion of HIV-inhibiting antibodies.Nature communications · 2025Article
- Deep Thought on the HIV Cured Cases: Where Have We Been and What Lies Ahead?Biomolecules · 2025Review
- Breaking Barriers to an HIV-1 Cure: Innovations in Gene Editing, Immune Modulation, and Reservoir Eradication.Life (Basel, Switzerland) · 2025Review
- In pursuit of an HIV cure: from stem cell transplants to gene therapies.Frontiers in genome editing · 2025Review
- CAR-T Therapy in HIV: Pioneering Advances and Navigating Challenges.Infectious diseases & immunity · 2024Article
- High-resolution Inference of Multiplexed Anti-HIV Gene Editing using Single-Cell Targeted DNA Sequencing.bioRxiv : the preprint server for biology · 2024Article
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8 authors.
Funding
Abstract
Allogeneic hematopoietic stem and progenitor cell transplant (HSCT) of CCR5 null (CCR5Δ32) cells can be curative for HIV-1-infected patients. However, because allogeneic HSCT poses significant risk, CCR5Δ32 matched bone marrow donors are rare, and CCR5Δ32 transplant does not confer resistance to the CXCR4-tropic virus, it is not a viable option for most patients. We describe a targeted Cas9/AAV6-based genome editing strategy for autologous HSCT resulting in both CCR5- and CXCR4-tropic HIV-1 resistance. Edited human hematopoietic stem and progenitor cells (HSPCs) maintain multi-lineage repopulation capacity in vivo, and edited primary human T cells potently inhibit infection by both CCR5-tropic and CXCR4-tropic HIV-1. Modification rates facilitated complete loss of CCR5-tropic replication and up to a 2,000-fold decrease in CXCR4-tropic replication without CXCR4 locus disruption. This multi-factor editing strategy in HSPCs could provide a broad approach for autologous HSCT as a functional cure for both CCR5-tropic and CXCR4-tropic HIV-1 infections.
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