Blueprint to Engineering and Scaling LNPs for Clinical Development

mRNA therapeutics have become more commonplace after the two COVID vaccines. The contemporary delivery system for mRNA is Lipid Nanoparticles (LNPs). LNPs classically consist of an ionizable lipid, PEG lipid, phospholipid, and cholesterol. Unless designed otherwise, IV administered LNPs have a natural affinity to accumulate in the liver as apolipoprotein E (ApoE) generates a protein corona and plays a major role in hepatocellular LNP uptake via the LDLR receptor. There are strategies to avoid liver uptake for LNPs – they revolve around tailoring the composition of the LNP to reduce liver affinity, enhance alternate tissue tropism, and adding targeting ligands. Such a strategy will allow mRNA-loaded LNPs to be used, for example, for in vivo gene editing or CAR T cell generation in non-liver tissues.
This hot topic presentation will focus in on formulation design, development, process optimization for clinical development – it will start addressing the topic for LNP with a liver tropism but also dive into the added complexity that may come from LNPs incorporating additional components such as targeting ligand to direct LNPs outside the liver