Project Grant R15HL188200

The National Heart, Lung, and Blood Institute awarded the University of Pikeville, Inc. a Project Grant of $351,311 on September 1, 2026, under the Cardiovascular Diseases Research program (CFDA 93.837) to develop a plant-based production platform for nonglycosylated reteplase, a recombinant tissue plasminogen activator used for thrombolytic therapy in acute myocardial infarction.

The project will establish rapid, cost-effective manufacturing of bioactive reteplase using transient expression in Nicotiana benthamiana plants modified with a geminiviral vector. Reteplase will be directed to two non-glycosylating compartments—the cytosol to support yield and simplify recovery, and the chloroplast thylakoid lumen to promote correct disulfide bond formation and stability. Preliminary undergraduate-led work has demonstrated that plant-produced reteplase dissolves fibrin and human blood clots comparably to the commercial drug. Specific aims include designing and codon-optimizing reteplase constructs, expressing and biochemically validating reteplase in plant tissue, and functionally validating plant-derived reteplase in fibrin and whole-blood clot assays while scaling production using vacuum-based agroinfiltration. The expected outcome is a high-quality production platform without post-expression deglycosylation, addressing cost barriers that restrict access to thrombolytic therapy, particularly in Central Appalachia where heart disease mortality is 42 percent higher than the national average.

Place of performance is Pikeville, Kentucky. The period of performance runs through May 31, 2029.