May
Single-molecule and single-cell microscopy of mRNA-lipid-nanoparticles: applying nanoscale physics to advance nanomedicines
Seminar by Sabrina Rose Leslie, Associate Professor, UBC Department of Physics and Astronomy and Michael Smith Labs
In response to the pandemic, new mRNA-LNP products were developed and injected into billions of human arms. Despite the success of these nanomedicines in suppressing the pandemic at the level of the population, at the level of the individual particle the efficiency of this product is less than a few percent. This presents an important opportunity for microscopists and therapeutic developers to work together to improve these products and to create a vast array of new nanomedicines ranging from COVID19 vaccines to cancer treatments. In this talk, I will present quantitative single-particle and single-cell investigations of mRNA LNPs which make use of the CLiC (Convex Lens-induced Confinement) microscopy technique, which we have pioneered and applied to study the interactions of single molecules and particles, without tethers and in cell-like conditions. Here, CLiC imaging enables simultaneous single-particle measurements of multiple properties of mRNA LNPs, such as the distribution of size and mRNA-payload, as well as interaction rates in response to changes in solution conditions and other molecules. Importantly these single-particle measurements can be made in correlation with observations of their dynamic trajectories and interactions within cells. This research is collaborative with Prof. Pieter Cullis and the Nanomedicine Center for Excellence based at UBC and aims to characterize and understand the mechanisms of action of emerging classes of therapeutics and vaccines, so as to ultimately enable their optimization and come closer to addressing patients’ needs. For example, we introduce a new approach to imaging the properties of individual confined, freely diffusing mRNA LNPs during a dynamic change in solution pH, which is relevant to understanding mRNA LNP delivery in cells as well as aspects of their manufacturing. Over the long term and in collaboration with health scientists, we are working towards correlating our detailed multi-scale data sets, including single-particle measurements made in vitro as well as in cells and tissues, with clinical results, to create a through-line of understanding of vaccine/drug effectiveness from the microscopic to clinical scale. This talk will begin with our publications in ACS Nano (Kamanzi et al, 2021, 2023), share results from two additional manuscripts in review and preparation, and describe our ongoing collaboration with health scientists to better understand mRNA-LNP vaccines and medicines through new biophysical measurements.
About the event
Location:
k-space, Fys:Q179
Contact:
heiner [dot] linke [at] ftf [dot] lth [dot] se