ArticleMolecular therapy : the journal of the American Society of Gene Therapy2012
Zinc-finger nuclease editing of human cxcr4 promotes HIV-1 CD4(+) T cell resistance and enrichment.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 103 citations in OpenAlex.
- Searching for a HIV-1 Cure.Theranostics · 2026Review
- Prospects of viral vector-mediated delivery of sequences encoding anti-HBV designer endonucleases.Gene therapy · 2025Review
- Humanized Mice for Studies of HIV-1 Persistence and Elimination.Pathogens (Basel, Switzerland) · 2023Review
- A lentiviral vector B cell gene therapy platform for the delivery of the anti-HIV-1 eCD4-Ig-knob-in-hole-reversed immunoadhesin.Molecular therapy. Methods & clinical development · 2023Article
- Closing the Door with CRISPR: Genome Editing of CCR5 and CXCR4 as a Potential Curative Solution for HIV.Biotech (Basel (Switzerland)) · 2022Review
- HIV cure strategies: which ones are appropriate for Africa?Cellular and molecular life sciences : CMLS · 2022Review
- Therapeutic Application of Genome Editing Technologies in Viral Diseases.International journal of molecular sciences · 2022Review
- CRISPR-Cas9-mediated gene disruption of HIV-1 co-receptors confers broad resistance to infection in human T cells and humanized mice.Molecular therapy. Methods & clinical development · 2022Article
- Application of CRISPR/Cas Genomic Editing Tools for HIV Therapy: Toward Precise Modifications and Multilevel Protection.Frontiers in cellular and infection microbiology · 2022Review
- Editing out HIV: application of gene editing technology to achieve functional cure.Retrovirology · 2021Review
- Genetic engineering of T cells for immunotherapy.Nature reviews. Genetics · 2021Review
- Knowledge From London and Berlin: Finding Threads to a Functional HIV Cure.Frontiers in immunology · 2021Review
- Humanized Mice for the Evaluation of Novel HIV-1 Therapies.Frontiers in immunology · 2021Review
- Review
- CCR5 editing by Staphylococcus aureus Cas9 in human primary CD4Retrovirology · 2019Article
- The Signaling Pathways, and Therapeutic Targets of Antiviral Agents: Focusing on the Antiviral Approaches and Clinical Perspectives of Anthocyanins in the Management of Viral Diseases.Frontiers in pharmacology · 2019Review
- Application of CRISPR/Cas9-Based Gene Editing in HIV-1/AIDS Therapy.Frontiers in cellular and infection microbiology · 2019Review
- Modulated expression of the HIV-1 2LTR zinc finger efficiently interferes with the HIV integration process.Bioscience reports · 2018Article
- Genome editing for the treatment of tumorigenic viral infections and virus-related carcinomas.Frontiers of medicine · 2018Review
- One-Vector System for Multiplexed CRISPR/Cas9 against Hepatitis B Virus cccDNA Utilizing High-Capacity Adenoviral Vectors.Molecular therapy. Nucleic acids · 2018Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
HIV-1-infected individuals can harbor viral isolates that can use CCR5, as well as CXCR4, for viral entry. To genetically engineer HIV-1 resistance in CD4(+) T cells, we assessed whether transient, adenovirus delivered zinc-finger nuclease (ZFN) disruption of genomic cxcr4 or stable lentiviral expression of short hairpin RNAs (shRNAs) targeting CXCR4 mRNAs provides durable resistance to HIV-1 challenge. ZFN-modification of cxcr4 in CD4(+) T cells was found to be superior to cell integrated lentivirus-expressing CXCR4 targeting shRNAs when CD4(+) T cells were challenged with HIV-1s that utilizes CXCR4 for entry. Cxcr4 disruption in CD4(+) T cells was found to be stable, conferred resistance, and provided for continued cell enrichment during HIV-1 infection in tissue culture and, in vivo, in peripheral blood mononuclear cell transplanted NSG mice. Moreover, HIV-1-infected mice with engrafted cxcr4 ZFN-modified CD4(+) T cells demonstrated lower viral levels in contrast to mice engrafted with unmodified CD4(+) T cells. These findings provide evidence that ZFN-mediated disruption of cxcr4 provides a selective advantage to CD4(+) T cells during HIV-1 infection.
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Registered trials
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