Speaker
Description
HIV remains a major global health challenge because antiretroviral therapy (ART) suppresses active virus but cannot eliminate the latent reservoir of infected CD4+ T cells, which can persist for years and reignite infection if treatment stops. New strategies are therefore needed to address viral latency. This theory project explores the use of DNA strand displacement (DSD) circuits to autonomously control the timing and sequence of drug delivery for chronic infections such as HIV. Using simulations, we couple a programmable ten-stage molecular release circuit to a mechanistic HIV disease model that tracks uninfected, infected, and latently infected CD4+ T cells, free virus, and drug concentrations. The model incorporates both ART and latency-reversing agents (LRAs). We integrate a sequential DSD circuit that acts as a molecular controller, releasing payloads that activate latent virus, deliver ART, or pause treatment based on therapeutic effectiveness. In simulation, this system can implement a “shock and kill” strategy by activating latent reservoirs, evaluating multiple drug options, and continuing the most effective treatment until the reservoir is reduced, after which the circuit remains dormant but responsive. These results suggest that programmable DSD timing circuits could enable autonomous, patient-specific therapies for HIV and other diseases requiring long-term, staged interventions.
