From: 2024-05-21 16:15 to 17:00
Place: k-space, Fys:Q179, LU
Contact: emma [dot] sparr [at] fkem1 [dot] lu [dot] se

A COMMONS seminar by visiting professor Sabrina Leslie USB Vancouver

Title: Single-molecule and single-cell microscopy of mRNA-lipid-nanoparticles: 
applying nanoscale physics to advance nanomedicines
Time: 21/05 16:15-17:00
Place: k-space, Fys:Q179, LU
https://lu-se.zoom.us/j/67689620156
Abstract:
n 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.