ArticleMolecular therapy. Nucleic acids2015
Combined Antiviral Therapy Using Designed Molecular Scaffolds Targeting Two Distinct Viral Functions, HIV-1 Genome Integration and Capsid Assembly.
Article in Molecular therapy. Nucleic acids, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- CRISPR/Cas9 genome editing of CCR5 combined with C46 HIV-1 fusion inhibitor for cellular resistant to R5 and X4 tropic HIV-1.Scientific reports · 2024Article
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- Specific Interaction of DARPin with HIV-1 CAViruses · 2022Article
- Engineered Zinc Finger Protein Targeting 2LTR Inhibits HIV Integration in Hematopoietic Stem and Progenitor Cell-Derived Macrophages: In Vitro Study.International journal of molecular sciences · 2022Article
- Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production.Biomolecules · 2021Article
- 2LTRZFP Interacts Specifically to HIV-1 DNA without Off-Target Effects as Determined by Biolayer Interferometry.Biosensors · 2021Article
- Occupation of a thermoresistant-scaffold (αRep) at SP1-NC cleavage site disturbs the function of HIV-1 protease.Bioscience reports · 2020Article
- Article
- Modulated expression of the HIV-1 2LTR zinc finger efficiently interferes with the HIV integration process.Bioscience reports · 2018Article
- Modeling Anti-HIV-1 HSPC-Based Gene Therapy in Humanized Mice Previously Infected with HIV-1.Molecular therapy. Methods & clinical development · 2018Article
- Alpha-helicoidal HEAT-like Repeat Proteins (αRep) Selected as Interactors of HIV-1 Nucleocapsid Negatively Interfere with Viral Genome Packaging and Virus Maturation.Scientific reports · 2017Article
- Current Peptide and Protein Candidates Challenging HIV Therapy beyond the Vaccine Era.Viruses · 2017Review
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 3 countries.
Funding
Abstract
Designed molecular scaffolds have been proposed as alternative therapeutic agents against HIV-1. The ankyrin repeat protein (Ank(GAG)1D4) and the zinc finger protein (2LTRZFP) have recently been characterized as intracellular antivirals, but these molecules, used individually, do not completely block HIV-1 replication and propagation. The capsid-binder Ank(GAG)1D4, which inhibits HIV-1 assembly, does not prevent the genome integration of newly incoming viruses. 2LTRZFP, designed to target the 2-LTR-circle junction of HIV-1 cDNA and block HIV-1 integration, would have no antiviral effect on HIV-1-infected cells. However, simultaneous expression of these two molecules should combine the advantage of preventive and curative treatments. To test this hypothesis, the genes encoding the N-myristoylated Myr(+)Ank(GAG)1D4 protein and the 2LTRZFP were introduced into human T-cells, using a third-generation lentiviral vector. SupT1 cells stably expressing 2LTRZFP alone or with Myr(+)Ank(GAG)1D4 showed a complete resistance to HIV-1 in viral challenge. Administration of the Myr(+)Ank(GAG)1D4 vector to HIV-1-preinfected SupT1 cells resulted in a significant antiviral effect. Resistance to viral infection was also observed in primary human CD4+ T-cells stably expressing Myr(+)Ank(GAG)1D4, and challenged with HIV-1, SIVmac, or SHIV. Our data suggest that our two anti-HIV-1 molecular scaffold prototypes are promising antiviral agents for anti-HIV-1 gene therapy.
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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.