Lipid Nanoparticles for RNA Delivery Beyond the Liver

Abstract

Lipid nanoparticles (LNPs) have transformed the field of RNA therapies by facilitating the targeted delivery of nucleic acids to hepatocytes, but a key challenge is to broaden their use to other tissues. The presented review discusses logistical planning approaches, mechanistic understanding, and translational advantage of LNPs adjusted to be delivered to other tissues other than the liver. The issue of critical targeting of organs (such as lipid composition, particle size, surface charge, and selective organ targeting, SORT), is examined. Preclinical data demonstrate successful delivery to lungs, spleen, and kidneys, and overcome biological barriers, immune clearance and off-target effects. The design principles of rational design, quality-by-design and future of clinical translation are also addressed in the review. The increase in the multi-organ RNA delivery versatility among LNPs is also promising to widen the applicability of therapy in genetic, inflammatory, as well as infectious diseases.