ArticleMolecular therapy : the journal of the American Society of Gene Therapy2013
Generation of an HIV resistant T-cell line by targeted "stacking" of restriction factors.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 73 citations in OpenAlex.
- A simultaneous knockout knockin genome editing strategy in HSPCs potently inhibits CCR5- and CXCR4-tropic HIV-1 infection.Cell stem cell · 2024Article
- Generation of hepatitis C virus-resistant liver cells by genome editing-mediated stable expression of RNA aptamer.Molecular therapy. Methods & clinical development · 2023Article
- Gene Therapy for Cardiovascular Disease: Basic Research and Clinical Prospects.Frontiers in cardiovascular medicine · 2021Review
- Corrigendum: Targeted Gene Delivery: Where to Land.Frontiers in genome editing · 2021Article
- Engineering precision therapies: lessons and motivations from the clinic.Synthetic biology (Oxford, England) · 2021Review
- Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects.Signal transduction and targeted therapy · 2020Review
- Targeted Gene Delivery: Where to Land.Frontiers in genome editing · 2020Review
- Development of Lentiviral Vectors for HIV-1 Gene Therapy with Vif-Resistant APOBEC3G.Molecular therapy. Nucleic acids · 2019Article
- CRISPR/Cas system: An emerging technology in stem cell research.World journal of stem cells · 2019Review
- Bioengineering Solutions for Manufacturing Challenges in CAR T Cells.Biotechnology journal · 2018Review
- Review
- Multiplexed genetic engineering of human hematopoietic stem and progenitor cells using CRISPR/Cas9 and AAV6.eLife · 2017Article
- Genome-Edited T Cell Therapies.Current stem cell reports · 2017Review
- Clinical Applications of Genome Editing to HIV Cure.AIDS patient care and STDs · 2016Article
- A Cas9 Ribonucleoprotein Platform for Functional Genetic Studies of HIV-Host Interactions in Primary Human T Cells.Cell reports · 2016Article
- Review
- Genome-editing Technologies for Gene and Cell Therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Review
- Mechanistic Models Predict Efficacy of CCR5-Deficient Stem Cell Transplants in HIV Patient Populations.CPT: pharmacometrics & systems pharmacology · 2016Article
- Creation of chimeric human/rabbit APOBEC1 with HIV-1 restriction and DNA mutation activities.Scientific reports · 2016Article
- Towards a new era in medicine: therapeutic genome editing.Genome biology · 2015Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Restriction factors constitute a newly appreciated line of innate immune defense, blocking viral replication inside of infected cells. In contrast to these antiviral proteins, some cellular proteins, such as the CD4, CCR5, and CXCR4 cell surface receptors, facilitate HIV replication. We have used zinc finger nucleases (ZFNs) to insert a cocktail of anti-HIV restriction factors into the CCR5 locus in a T-cell reporter line, knocking out the CCR5 gene in the process. Mirroring the logic of highly active antiretroviral therapy, this strategy provides multiple parallel blocks to infection, dramatically limiting pathways for viral escape, without relying on random integration of transgenes into the genome. Because of the combination of blocks that this strategy creates, our modified T-cell lines are robustly resistant to both CCR5-tropic (R5-tropic) and CXCR4-tropic (X4-tropic) HIV-1. While zinc finger nuclease-mediated CCR5 disruption alone, which mimics the strategy being used in clinical trials, confers 16-fold protection against R5-tropic HIV, it has no effect against X4-tropic virus. Rhesus TRIM5α, chimeric human-rhesus TRIM5α, APOBEC3G D128K, or Rev M10 alone targeted to CCR5 confers significantly improved resistance to infection by both variants compared with CCR5 disruption alone. The combination of three factors targeted to CCR5 blocks infection at multiple stages, providing virtually complete protection against infection by R5-tropic and X4-tropic HIV.
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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.