Grant: Research Tools and Instruments

Research on extracellular vesicles (EVs) and nanoparticles has radically advanced. We discovered that EVs can be efficient at delivering cargoes into recipient cells, elevating the hypothesis that EVs are an evolved intercellular communication system. How EVs are produced, packaged with selective cargoes, and deliver their cargoes into particular cell types in vivo is a subject of intense investigation. The capacity of EVs to deliver cargoes is also being appropriated for drug delivery. Lipid nanoparticles enable the use of nucleic acid therapeutics in patients, including SARS-CoV2 vaccines, silencing RNA therapeutics, and CRISPR gene-editors in late-stage clinical trials. While these are successful in delivering nucleic acids locally (vaccines), or to the liver (siRNA, CRISPR), more efficient, less toxic ones are required for use in organs like kidney, lung, heart or brain. The heterogeneity of EV and nanoparticle populations is critical to understand. Small EVs can be produced through alternative pathways including ESCRT-, ceramide-, Arrestin- or Syntenin-dependent ones. Small EVs are often found with larger (microvesicles, apoptotic bodies) or smaller (HDL, exomeres) particles. Similarly, most nanoparticle preparations are heterogenous populations of functional and non-functional particles. Size and markers such as lipid vs. drug cargo, or markers of sEV subpopulations are critical to study their biology and develop them as delivery vehicles. Nanoparticle Tracking Analyzers (NTA) are a crucial technology to study EVs and nanoparticles. The Particlemetrix Zetaview Twin enables the capture of the size, charge, and multiple fluorescent markers for each of thousands of particles in 1 minute. This data and its speed and simplicity cannot be achieved with super-resolution microscopes or flow cytometers. The Gibbings, Berezovski and Gadde labs and 70 HQP in Ottawa have been intensively using an NTA for their research for the past 8 years. It has been crucial to several papers published by these labs and others, patents and industry collaborations, but the current instrument has broken. This leaves them without the only robust and time-effective method to validate every EV or nanoparticle they prepare and has dramatically impaired their research progress. With the acquisition of a new NTA the applicants will expand the pool of HQPs users. HQP trained in the applicants' labs have a track record of winning competitive national scholarships, publishing in high quality journals, and attaining rewarding careers in their fields. Training in these labs with the NTA they acquire expertise in fields of great interest in academia, biotech and pharma industries. The applicants work frequently with industry and promote entrepreneurship providing HQP additional pathways into jobs. The applicants are committed to the principles of EDI and have multi-faceted initiatives in their labs and institution to address EDI on the many fronts it permeates our systems.