Roadmap to Designing and Selecting LNPs for mRNA Drug Delivery

mRNA therapeutics are a new modality, and before the two COVID vaccines were launched, it was a niche area in drug development. Now they have emerged as a therapeutic modality option front and center to R&D, of course in vaccine development but also for non-viral gene therapies, in vivo CAR T cell therapies and protein replacement with many opportunities in company pipelines. However, mRNA is large, charged, easily degraded by nucleases. It can’t get into cells, escape the endosome and be translated to a desirable disease-modifying protein in the cytosol without a delivery system. Lipid nanoparticles (LNPs) is the contemporary delivery system of choice for this purpose.

LNPs on the market are covered by IP and hence companies pursuing mRNA modalities are usually aiming to “buy” or “build” their own delivery system. The many opportunities to license a LNP is outside the scope of this presentation, and the focus is to provide guidance on how to build such a LNP drug delivery system internally. The presentation will both cover science elements as well as strategies for success.

Classical LNPs are 4 component systems (Ionizable lipid, PEG lipid, phospholipid & cholesterol), and the session will dive into how one can design such a new LNP. It will cover elements such as excipients design, automated screening approaches, in vitro and in vivo studies. Case studies will be shared to complement the principles. The session will also feature strategies for incorporating early development considerations into designing the delivery system in discovery to ensure a smooth path to the clinic.

Unless special design or targeting efforts are applied most LNP designs will end up in the liver, and the session will end with a perspective on how we may target other tissues of interest.