National Institute of Mental Health 5R01MH128155-05

Novel macrophage-tropic transmitted/founder SHIV model of CNS persistence to evaluate CRISPR/Cas9 gene editing

The award funds research to develop an animal model of HIV persistence in the brain and to test CRISPR/Cas9 gene editing as a potential cure strategy for HIV. The project uses advanced SHIV models and gene editing techniques to study and target the CNS reservoir of HIV.

Description

This project aims to develop a robust model for HIV pathogenesis and persistence in the brain, and evaluate the safety and efficacy of a CRISPR-based cure strategy. Characterization of the CNS reservoir and empiric testing of novel cure strategies require physiologically relevant animal models of HIV persistence in the brain. The project integrates advances in transmitted/founder SHIV NHP models and AAV-delivered CRISPR/Cas9 editing to delineate key features of the CNS reservoir and assess a promising approach to eradicative cure. Coordinated NHP experiments will use barcoded, macrophage-tropic TF SHIV.D to elucidate mechanisms of CNS persistence and test efficacy of global and myeloid-specific CRISPR/Cas9 gene editing to cure HIV.

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