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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/35392
Title: Combined Antiviral Therapy Using Designed Molecular Scaffolds Targeting Two Distinct Viral Functions, HIV-1 Genome Integration and Capsid Assembly
Authors: Wannisa Khamaikawin
Somphot Saoin
Sawitree Nangola
Koollawat Chupradit
Supachai Sakkhachornphop
Sudarat Hadpech
Nattawat Onlamoon
Aftab A. Ansari
Siddappa N. Byrareddy
Pierre Boulanger
Saw See Hong
Bruce E. Torbett
Chatchai Tayapiwatana
Chiang Mai University
University of Phayao
Mahidol University
Emory University
Universite de Lyon
Scripps Research Institute
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 25-Aug-2015
Citation: Molecular Therapy - Nucleic Acids. Vol.4, (2015), e249
Abstract: Designed molecular scaffolds have been proposed as alternative therapeutic agents against HIV-1. The ankyrin repeat protein (AnkGAG1D4) 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 AnkGAG1D4, 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(+)AnkGAG1D4 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(+)AnkGAG1D4 showed a complete resistance to HIV-1 in viral challenge. Administration of the Myr(+)AnkGAG1D4 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(+)AnkGAG1D4, 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.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84940053734&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/35392
ISSN: 21622531
Appears in Collections:Scopus 2011-2015

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