Passcode: 123456

Faculty Advisor:
Michael E. Davis, PhD

Committee Members:
Manu Platt, PhD
Vahid Serpooshan, PhD
Hee Cheol Cho, PhD    
Julie Champion, PhD
 

Title: Engineering small extracellular vesicle-derived vehicles carrying optimized microRNA for cardiac repair after myocardial infarction 

Abstract: Myocardial infarction (MI) is one of the leading causes of morbidity and mortality worldwide. One promising therapy involves delivering small extracellular vesicles (sEVs), released from cardiac relevant cell types, to the infarct. These sEVs are 30-150nm vesicles containing protein and/or nuclear cargo. Despite their reparative potential, sEV therapies have several issues due to their cellular origin, including variable sEV yield and uncontrolled and low-density cargo encapsulation. Synthetic mimics (SUVs) have been developed which allow optimized cargo loading but these have high toxicity, compromised membranes and poor uptake. Therefore, there is a need for cell-free vehicles with sEV-like membrane and uptake, which allow delivery of higher concentrations of custom cargo. Our goal is to engineer such a vesicle to deliver tailored microRNA cargo, and induce cardiac repair post-MI. We hypothesize that sEV-like vesicles (ELVs) engineered using a natural membrane and loaded with customized cargo will improve cardiac tissue repair after MI compared to that of unmodified sEVs or SUVs. Aim 1 will focus on ELV synthesis and in vitro functional responses. Aim 2 will assess ELV potency in a rat MI model. Finally, Aim 3 will determine parent cell effects on ELV membrane composition and, in turn, ELV uptake and functionality.