Grant: Project Grant - PA: Infection and Immunity (Early Career Research Support)

Donated organs infected with incurable cytomegalovirus (CMV) are unsafe for transplant recipients. The goal of this project is to clear CMV from harvested organs. Clearance is achieved using a smart nanotechnology treatment that targets and destroys the virus' DNA from inside the infected organ's cells. CMV infects people all over the world. In healthy people, CMV symptoms are minimal; however, for people with suppressed immune systems, it can be deadly. Because organ transplant recipients have suppressed immune systems, this virus is a deadly threat. Refusing the use of CMV-infected lungs is an unrealistic and extreme measure that would reduce the number of available organs and increase transplant wait times. Alternatively, CMV can be partially controlled by certain drugs; however, new drug-resistant CMV strains are emerging. To increase the number of usable organs and shorten wait times, new treatments that destroy CMV infections are desperately needed. Gene-editing technologies that can enter sick cells and delete the infecting virus' essential genes are potential solutions. Normally, gene editing tools are delivered to cells using repurposed viruses. However, these repurposed viruses can pose their own safety risks and be difficult to manufacture. To address these unsolved challenges, our project engineers a safer and more efficient nanotechnology-based treatment. Nanoparticles designed to contain all the required gene editing tools are created and added to saline water. After an organ infected with CMV is harvested, this nanoparticle-water mixture is pumped through the organ. The nanoparticles circulate throughout the organ, enter the cells, and release their gene editing tools. The tools target any viruses inside and deletes sections of the virus' genes, rendering them harmless, which lessens the need for anti-CMV drugs. Thus, through our innovation, exceptional control, precision, efficacy and safety is achieved.