Project Lead

Dr Michael Moso


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.