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siRNA Lipid Nanoparticle Delivery for Liver Defatting During Normothermic Machine Perfusion

Enhancing the viability of fatty donor livers for transplantation

Full Project Name:siRNA Lipid Nanoparticle Delivery for Liver Defatting During Normothermic Machine PerfusionPrincipal Investigator:Joohyun Kim, MD, PhD, SurgeryCo-Investigator:Christian Kastrup, PhD, Surgery; Ze Zheng, PhD, MedicineAward Amount:$50,000
Award Date
January2024
Project Duration:12 months

Project Description Narrative:


End-stage liver disease (ESLD) is the eighth-leading cause of death in the United States, and the average life expectancy of patients is only two years. The economic burden is substantial, with annual direct costs exceeding $2 billion and indirect costs exceeding $10 billion. Liver transplantation (LT) represents the only life-saving therapeutic option for patients with ESLD.

More than 65,000 people in the United States are living with a transplanted liver. Meanwhile, approximately 12,000 people are still waiting for LT, and thousands of patients die annually while on the waiting list. However, significant numbers of donor organs have been declined for LT, and organ discard rates remain high despite a growing organ shortage. The reluctance to use grafts of marginal quality stems from fear of graft failure from ischemia-reperfusion injury (IRI) during the organ procurement and re-implantation process, which occurs after LT in about 5–8% of cases. Overall, the organ discard rate in the United States has increased during the past years, from 8.6% in 2018 to 10.0% in 2021. The trend may be explained by the increase in donations from donors with associated risk of IRI such as fatty change of the liver (hepatic steatosis).

This project team aims to defat livers for transplantation by removing excess fat to make the organ suitable for transplant. If successful, their approach will significantly increase available livers in Wisconsin, directly benefiting ESLD patients on the LT waiting list. By utilizing previously unsuitable organs, Wisconsin stands to realize considerable healthcare savings, offering economic and life-saving advantages.

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