Rapidly Test a Novel Therapeutic Strategy for COVID-19 in Human Organoids and Blood Vessel Structures
Abstract
Goal: The overall goal of this project is to establish a method to create antidotes for COVID-19 and related diseases in the future, to improve the readiness of our civilian and military populations. Background: The cinematic scenario in which a virus suddenly spreads across the globe and is in desperate need of an antidote is no longer science fiction. We are all living this scenario and understand first-hand how it impacts our lives. The United States has suffered more deaths from COVID-19 than any other country. We were unprepared for COVID-19. The premise behind this project is that this should never happen again. Approach: We propose to utilize 21st century technologies – artificial organs and artificial intelligence – to establish an “antidote lab” capable of rapidly developing therapies for COVID-19 and related diseases. This is all the more important when we consider that SARS-CoV-2, the virus that causes COVID-19, is one in a series of natural viruses. It is spread via airborne molecules, and is therefore a potential bioweapon – one that is very high profile. Future coronavirus pandemics may be inevitable. At the public health level, many changes have been made. Policies are now in place for social distancing and face masking. While inconvenient, a safer path has been forged, at least for COVID-19. But the picture is much murkier when it comes to a permanent solution – a medical treatment to prevent infection or relieve its effects. Viruses mutate and can be mutated. Vaccines may eventually be successfully developed for SARS-CoV-2, but even if they are, they will not confer immunity for the next version of the virus. And for that version, we may not have the luxury of time to wait for a vaccine. The effects could be devastating. But there is hope. Over the past decade, we have witnessed tremendous advances in technology. Drs. Freedman and Ruohola-Baker, the investigators who lead this team, pioneered methods to grow mini-organ structures from people’s own bodies, including kidney structures and blood vessels. At the same time, Dr. Ruohola-Baker and Dr. David Baker marshaled the power of computational design and artificial intelligence to create new forms of biomolecules that target and neutralize the most dangerous elements of several different diseases. Now, we plan to come together as a team, along with physicians and engineers, to combine these powerful technologies with a comprehensive plan to combat COVID-19 and establish a ready-to-use framework in which we can readily develop and rapidly test the antidotes of the future. Detailed Plans: We will prototype our therapy with two types of computationally designed, synthetic proteins, which we can produce in the lab: • A virus neutralizer nanoparticle that binds to a “spike” protein on the surface of the coronavirus and prevents it from entering cells • An anti-inflammatory nanoparticle that protects cells from the overactive immune system We will test these therapies out on three different types of synthetic tissue constructs, which we can also produce in the lab: blood vessels, mini-kidney organoids, and mini-lung organoids. Over 93% of patients that die from COVID-19 succumb to acute respiratory distress syndrome (ARDS) and septic shock. The pathophysiology of both ARDS and sepsis is marked by dysfunctional blood vessels, which leak protein-rich serum, promotes white blood cell recruitment, and elevates inflammatory markers. Moreover, sepsis is a systemic condition where patients often die from internal organ failure, including kidneys. There are no approved treatments for these conditions outside of saline, antibiotics, and mechanical ventilation. We are particularly interested in the veteran population, which is aging and frequently has cardiovascular, kidney, or other health issues that place it at risk for COVID-19. We will recruit a cohort of patients from the Puget Sound VA to derive cells (out of their urine) and chan
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110006
Entities
People
- Hannele Ruohola-Baker
Organizations
- United States Army
- University of Washington