Engineering Lipid Nanoparticles for mRNA Immunotherapy.

Abstract

Over the last decades, messenger RNA (mRNA) has emerged as a promising therapeutic modality, enabling the delivery of genetic instructions to cells for producing therapeutic proteins or antigens. As such, mRNA-based therapies can be developed for a wide range of conditions, including infections, cancer, metabolic disorders, and genetic diseases. Nevertheless, using mRNA therapeutically requires chemical modifications to reduce immunostimulatory effects and nanotechnology to prevent degradation and ensure intracellular delivery. Lipid nanoparticles (LNPs) have become the most effective delivery platform for mRNA therapeutics, which are primarily employed for vaccine purposes following local administration and hepatic applications following systemic administration. Here, we review the state-of-the-art LNP-mRNA technology and discuss its potential for immunotherapy. We first outline the requirements for mRNA to be used therapeutically, including the role of LNP-mediated delivery. Next, we highlight LNP-mRNA immunotherapy approaches for vaccination, immuno-oncology, and autoimmune disorders. In addition, we discuss challenges that are limiting LNP-mRNA's widespread use, including tunable biodistribution and immunostimulatory effects. Finally, we provide an outlook on how implementing approaches such as library screening and machine learning will guide the development of next-generation mRNA therapeutics.