A-106 Eradication of HIV; molecular therapeutic paths to a functional cure

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Abstract

The eradication of functional replicative HIV is within our collective grasp. Several emerging modes of targeted therapeutics, ranging from chimeric antigen receptor (CAR) T-cell targeted killing of virus infected cells to targeted genomic editing and/or excision of latent provirus, may prove promising with regards to eradicating the spread of functional HIV. We have recently developed 2 distinct molecular approaches that may facilitate the eradication of HIV. The first approach is the systemic activation of HIV followed by a polyvalent “swarm” of HIV-gp120 bi-specific CAR CD4+/CD8+ T-cells. Systemic activation of latent HIV can occur by removing anti-retroviral therapy (ART) and/or by targeted activation of provirus. To activate provirus we developed a biologically deliverable recombinant zinc finger protein activator (ZFP-362-VPR), that functionally activates HIV in an LTR directed and specific manner. Notably, ZFP-362-VPR can be used in combination with a swarm of differentially HIV-gp120 targeted bi-specific CAR CD4+/CD8+ T-cells, to specifically kill virus infected cells. A second approach to eradicate HIV is the targeted genomic editing and/or excision of integrated virus. The approach we describe here builds on biologically deliverable recombinant protein technologies to direct the excision and/or targeted mutations to loci in the provirus, ultimately rendering the virus nonreplicative. Collectively, these emerging molecular therapeutic strategies juxtaposed with current antiretroviral therapy may one day result in the eradication of HIV.

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