Sarah Klinnert (PhD student)
The main hurdle towards a cure of HIV-1 is the presence of the HIV-1 latent reservoir, which is defined as transcriptionally inactive, integrated HIV-1 proviruses that persist life-long in the human body, hidden from the immune system.
We aim to utilize the state-of-the-art CRISPR/Cas9 gene editing technology in two different strategies to uncover and eliminate these latently HIV-1 infected cells. In the first approach, we aim to activate the latent proviruses by using a CRISPR activation system. Thereby, we want to favor subsequent elimination of formerly latently infected cells and also of the reactivated virus by cytopathic viral effects, immune surveillance mechanisms, and antiretroviral therapy. Second, we seek to target different regions of HIV-1 to excise crucial viral genes and/or to introduce mutations to render the provirus replication defective. Both approaches will be combined with a retargeted adenoviral delivery system, which allows specific delivery into the major part of the latent reservoir, namely CD4+ resting memory T-cells.
This project is a collaborative effort together with Prof. Huldrych Günthard’s, Prof. Alexandra Trkola’s, and Prof. Andreas Plückthun’s groups (UZH).