Nanoparticle and gene therapy approaches to HIV cure

Antiretroviral therapy (ART) can suppress but not eliminate HIV infection due to the persistence of latent HIV in the form of integrated DNA. A modified version of CRISPR/Cas9 allows activation of transcription without DNA cleavage (CRISPRa), providing a potential mechanism for HIV elimination through viral reactivation. This project will evaluate HIV-reactivating RNAs using the CRISPR activation system, delivered to T cells using lipid nanoparticles (LNPs) to reactivate latently infected cells. Initial work will focus on testing potency of various HIV-reactivating LNPs in cell line models. Further experiments will aim to optimise the LNP vehicle to enhance uptake in resting CD4 T cells, the primary reservoir for latent HIV. Ex vivo testing of LNPs will then be performed on cells obtained from donors living with HIV on ART.