Gladstone Institutes scientists have rapidly pivoted the focus of their research labs to the novel virus, SARS-CoV-2. Specifically, they are leveraging their established tools, unique infrastructure, and diverse expertise in virology to develop improved diagnostics, identify targeted treatment strategies, and invent preventative approaches.
Gladstone scientists were instrumental in converting HIV/AIDS from a uniformly lethal disease into a chronic condition, and are now bringing the same urgency and focus to combatting COVID-19 in a comprehensive manner.
Jennifer Doudna, PhD, co-inventor of CRISPR technology, and virologist Melanie Ott, MD, PhD, are collaborating to develop a CRISPR-based method to rapidly measure COVID-19 RNA. By combining the technique with iPhone technology, they aim to develop a diagnostic that could deliver rapid results and be widely deployed even far from traditional labs, such as in airports and other ports of entry, and in remote communities throughout the world.
Nevan Krogan, PhD, focusing on treatment, has discovered all of the human host cell proteins that the virus interacts with to hijack the cell’s machinery. These proteins serve as novel targets for drug therapies. Since the high fatality rate is driven by respiratory and cardiac failure, Melanie Ott, Bruce Conklin, MD, and Todd McDevitt, PhD, will test effects of the virus and drug candidates in human lung “organoids” and human heart cells, both developed from human stem cells. Virologist Warner Greene, MD, PhD, is reconfiguring an HIV entry/fusion assay to study entry of the virus into host cells mediated by the Spike protein of SARS-CoV-2. His team will screen a library of FDA-approved drugs to identify those that could be rapidly repurposed as a treatment for COVID-19 patients or even as a preventive for high risk-groups. The assay could also be used to select the best plasma samples donated by people who have recovered from COVID-19 for infusion into seriously ill patients.
Leor Weinberger, PhD, focus on prevention, has pioneered an innovative approach to fighting the spread of viral pathogens called therapeutic interfering particles (TIPs), which could be an alternative to a vaccine. TIPs are defective viral particles that mimic the virus but are ineffective in replicating. They turn the tables on the virus by hijacking its machinery to transform virus-infected cells into factories that produce even more therapeutic particles, amplifying the effect of TIPs in stopping the spread of virus. TIPs targeting COVID-19 would transmit along the same paths as the virus itself, and thus provide protection to even the most vulnerable populations.
This work is made possible in part because Gladstone has biosafety level 3 (BSL-3) facilities on-site, which are now dedicated to work on COVID-19. The BSL-3 research will be overseen by Melanie Ott, in partnership with UC San Francisco and its Institutional Biosafety Committee and Director of High Containment Laboratories.