This proposal is to develop engineered exosome CRISPR/saCas9 cargo to target HIV genomes and program exosome delivery to latently-infected cell types for HIV eradication.

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 DESCRIPTION (provided by applicant: HIV-1 continues to be a world-wide health problem with an estimated incidence of ~50,000 new cases each year in the United States alone. While antiretroviral therapy has changed the face of HIV infection from terminal illness to a chronic manageable disease, it does not restore a normal immune function or lifespan in infected subjects. A cure to permanently eliminate the virus from the body is yet to be found. HIV can remain latent in several sites within the body including the CNS where it establishes viral reservoirs and continues to persist despite treatment. A targeted genome editing approach that allows for precise and efficient deletion of integrated HIV DNA from the infected cell will be a significant advancement toward HIV cure. We propose to develop engineered exosomes loaded with CRISPR/Cas9 genome editing machinery designed to target integrated HIV DNA in latently-infected cells. These engineered exosomes will also be programmed using surface ligand display technologies to address the vesicles to adhere and deliver the cargo to cell types of interest. The overall goal of this project is to create a system where personalized exosome shuttles can be utilized as therapeutic delivery vehicles to eradicate HIV in viral cellular reservoirs.