Federal Project Grant Award Summary

Case Western Reserve University's Office of Research Administration received a $1.53 million Project Grant from the National Heart, Lung, and Blood Institute (NHLBI) under the Cardiovascular Diseases Research program (CFDA 93.837), awarded July 1, 2026, with completion targeted for May 31, 2028. The award funds research and development of a novel "bait-and-switch" gene therapy delivery platform designed to overcome critical barriers in adeno-associated virus (AAV)-based treatment of genetic cardiomyopathies, particularly hypertrophic cardiomyopathy (HCM). The research will deliver preclinical and translational research services including characterization of immunomodulatory nanoparticle design parameters, demonstration of disease reversal in murine HCM models, and evaluation of cardiac transduction efficiency in porcine models to establish translational feasibility.

The core innovation addresses hepatic sequestration of AAV vectors by employing nanoparticles that block Kupffer cell-mediated clearance in the liver while enhancing myocardial tropism through transient cardiac glycosylation, potentially enabling 10- to 100-fold dose reductions. This platform-based approach decouples therapeutic efficacy from vector capsid engineering, enabling heart-targeted delivery of any therapeutic transgene without modification. Upon successful completion, the research is expected to unlock clinical viability for AAV-based therapies across genetic cardiomyopathies, addressing conditions where up to 40 percent of patients experience heart failure mortality by mid-adulthood.