RNA therapeutics is a 60 year work in progress. Beyond mRNA the many types of RNA in cells and tissues, means that it can be drug and/or target with many new therapeutic applications emerging. Unlike oligonucleotides, larger RNA macromolecules require nanoparticle to resist RNase degradation, increase intracellular uptake and in vivo delivery. Lipid nanoparticle (LNP) while first through the clinic, generally suffer from low RNA payloads, temperature instability and liver clearance limiting their application. Polymer/peptide/protein (PNP) or metal nanoparticle (MNP) may help solve these challenges. Further, self-amplifying RNA (saRNA) or replicon RNA (repRNA) can increase expression, safety and potency. These can encode multiple antigens or therapeutic protein, potentially offering universal flu or COVID vaccine for example. Yet these are longer and much less stable, requiring further formulation and process innovation. This presentation will discuss current state-of-the-art for preparing RNA nanoparticles in their progress from pre-clinical to clinical trials.
Learning Objectives:
Describe the different classes of therapeutic RNA in development
