Loading and release of RNA for COVID-19 vaccines: direct visualization of lipid nanoparticle delivery vehicles.

点击翻译按钮获取中文摘要

The coronavirus pandemic has created an immediate need for Covid-19 vaccines and therapies. Several companies have developed vaccines which are already in clinical trials, where lipid nanoparticles (LNPs) are used to deliver RNA to target cells in humans. Here they stimulate the production of a single viral protein which elicits an immune response. RNA-based vaccines are potentially safer, cheaper, and lower dose than other vaccines, and can be manufactured fast enough to respond to the kind of global pandemic in which we find ourselves today. This is a completely new vaccine technology and there is much to learn and optimize about its mode of action. Our proposal aims to visualize the interactions of RNA with LNP delivery vehicles, characterizing the structure and RNA-carrying capacity of LNPs, in order to better understand and control the delivery of these therapeutic compounds to targeted cells in the body. Precision Nanosystems Inc (PNI) has developed the LNP delivery platform technology used by pharmaceutical companies in their development of vaccines and other Covid-19 therapeutics. The Leslie Lab at McGill University has developed a novel single-particle imaging technique called Convex Lens-induced Confinement ("CLiC"), which enables direct imaging of individual nanoparticles and molecules as they interact in solution. Our collaboration combines two made-in-Canada technologies to accelerate the development of Covid-19 vaccines. Using CLiC microscopy to study PNI's nanoparticle delivery technology, we can make new discoveries about the structure of LNPs, how they interact with RNA cargo, and how they deliver RNA to cells. CLiC can yield more detailed information than current techniques can provide, so we will gain insights into LNP behavior that were previously unattainable. Our research will create new tools and allow vaccine developers to design and optimize RNA-based therapeutics more efficiently, bringing much needed therapies more quickly to market.