Recent Advances in Lipid Nanoparticles and Their Safety Concerns for mRNA Delivery

Jialiang Wang; Yaopeng Ding; Kellie Chong; Meng Cui; Zeyu Cao; Chenjue Tang; Zhen Tian; Yuping Hu; Yu Zhao; Shaoyi Jiang

doi:10.3390/vaccines12101148

Recent Advances in Lipid Nanoparticles and Their Safety Concerns for mRNA Delivery

Vaccines (Basel). 2024 Oct 8;12(10):1148. doi: 10.3390/vaccines12101148.

Authors

Jialiang Wang¹, Yaopeng Ding¹, Kellie Chong², Meng Cui³, Zeyu Cao³, Chenjue Tang¹, Zhen Tian⁴, Yuping Hu², Yu Zhao¹, Shaoyi Jiang¹

Affiliations

¹ Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA.
² Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY 14853, USA.
³ Department of Materials Science and Engineering, Cornell University, Ithaca, NY 14853, USA.
⁴ Department of Biological and Environmental Engineering, Cornell University, Ithaca, NY 14853, USA.

Abstract

The advent of lipid nanoparticles (LNPs) as a delivery platform for mRNA therapeutics has revolutionized the biomedical field, particularly in treating infectious diseases, cancer, genetic disorders, and metabolic diseases. Recent Advances in Therapeutic LNPs: LNPs, composed of ionizable lipids, phospholipids, cholesterol, and polyethylene glycol (PEG) lipids, facilitate efficient cellular uptake and cytosolic release of mRNA while mitigating degradation by nucleases. However, as synthetic entities, LNPs face challenges that alter their therapeutic efficacy and safety concerns. Toxicity/Reactogenicity/Immunogenicity: This review provides a comprehensive overview of the latest advancements in LNP research, focusing on preclinical safety assessments encompassing toxicity, reactogenicity, and immunogenicity. Summary and Outlook: Additionally, it outlines potential strategies for addressing these challenges and offers insights into future research directions for enhancing the application of LNPs in mRNA therapeutics.

Keywords: endosomal escape; immunogenicity; lipid nanoparticle; reactogenicity; selective organ-targeting LNP; toxicity.

Publication types

Review

Grants and funding

We acknowledge financial support from the National Institute of Allergy and Infectious Diseases (R01 AI178125), the National Cancer Institute (U54 CA272688), and the start-up support from Cornell University, including the Robert Langer ’70 Family and Friends Professorship and the Cornell NEXT Nano Initiative.