Collaborative Grant: Towards a cure for AIDS in the SIV/rhesus macaque model

There is currently no cure for HIV and vaccine development has proved challenging. Patients are able to manage their disease with the use of highly active antiretroviral therapy (HAART), which has had a positive impact on reducing HIV morbidity and mortality. As with HIV infection in humans, infection with Simian Immunodeficiency Virus (SIV) in rhesus macaques is lifelong due to infected cells that lie dormant in the DNA of the virus that is integrated into the host DNA. Recent developments with new molecular tools, specifically CRISPR/Cas, have facilitated genome or DNA editing, making possible the removal of integrated provirus DNA from infected cells. We have designed genetically modified molecules that target conserved regions of the SIV genome, and showed that several of these edited molecules completely inhibit SIV replication in an in vitro (petri dish) system. Further studies indicate these cells can be directed to specific target cells, and future studies will try to show in an animal model that genetically modified cells could provide a new therapeutic treatment for reduction of the virus that lies dormant.