Förståelse av lipida nanopartikel struktur och endosomal flykt genom fosfolipasinteraktioner för att avancera design och funktionalitet av nanomediciner

Since their usage in COVID-19 vaccines, lipid nanoparticle (LNP) – RNA therapies are being investigated for many critical illnesses including cancer.

A key challenge in developing LNP therapeutics is to understand the mechanisms behind the cellular processing of LNPs and how their structure evolves during these processes.

There are indications that lipid biophysics principles may drive LNP function but a lack of structural characterisation tools has prevented extensive structure - function investigations.

This project uses my expertise in lipid biophysics to combine novel fluorescence assays, small angle X ray / neutron scattering and CryoEM to generate tools for the 3D reconstruction of LNPs and to determine the location of individual lipid components.

The tools will be used to probe LNP interactions with a lipid modifying enzyme (phospholipase D, PLD) involved in intracellular trafficking and understand how this impacts LNP fusion with the endosomal membrane.

I have engineered an extensive LNP structure library with defined LNP morphologies which will be used to study these interactions.

This will provide mechanistic insights into the LNP structure/function relationship that drives the PLD interaction and will be correlated to functional outcomes in breast cancer cells.

The award of this grant will enable me to establish my research group using lipid biophysics approaches to understand LNP cellular processing and to provide a platform for rational design of nanomedicines.