OM-Vate: A Platform for Elevating OMV-Based Drug Packaging & Delivery

Life-saving surgical procedures are deemed safe because we have antimicrobial drugs to fight dangerous infections. However, as microbes like bacteria are exposed to antimicrobials, they evolve to select traits that allow them to persist against these antimicrobials, rendering them ineffective. This is antimicrobial resistance, and it is a leading cause of death around the world.
Antimicrobial resistance directly causes the death of 1.27 million people, and contributed to 4.95 million deaths in 2019. This global issue affects all countries at all income levels. It puts our medical progress at risk, increasing the lethal risk of infections for patients. This global problem is further exacerbated by bottlenecks in drug development, with only two new classes of antimicrobials being introduced in the past 30 years.
Since the rate of drug development cannot keep up with the rate of resistance, we propose a novel targeted delivery method which combines OMVs and antimicrobial peptides to remove resistance mechanisms.
A major extrinsic resistance mechanism is biofilm formation. Biofilms are created by ESKAPE pathogens, which prevent antimicrobials from penetrating resistant bacteria, concentrating bacteria together, and enabling bacteria to share resistance genes. OMVs exist in naturally occurring biofilms, and the extracellular matrix is not evolved to block them. As opposed to conventional drug delivery systems, OMVs also effectively protect therapeutic cargo against low pH microenvironments and physical barriers. Through engineering bacteria strains compatible with the human gut, we can package and deliver antimicrobial peptides, bypassing the biofilm and disrupting bacterial persistence. Other delivery methods, like viral vectors, are constrained by narrow host range, variable bacterial susceptibility, limited stability at target sites, and risks of unintended genetic changes. Our prototype overcomes these limitations, removes resistance mechanisms and ensures existing antimicrobials remain effective.
Our system uses the vesicle nucleating protein (VNp) to promote the packaging of therapeutic cargo into vesiculating OMVs. By fusing the VNp sequence to antimicrobial peptides, we can engineer bacteria to produce cargo-containing OMVs in situ, offering localized, targeted drug delivery. This platform aims to create a scalable and modular OMV delivery system capable of targeting resistant biofilm-forming pathogens while enabling broader applications in therapeutics, vaccines, and biotechnology.