Difference in the lipid nanoparticle technology employed in three approved siRNA (Patisiran) and mRNA (COVID-19 vaccine) drugs

• Published in: Drug metabolism and pharmacokinetics Vol. 41; p. 100424
• Main Authors: Suzuki, Yuta, Ishihara, Hiroshi
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2021; The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd
• Subjects: Animals; COVID-19; COVID-19 - immunology; COVID-19 vaccine moderna; COVID-19 Vaccines - immunology; Elasomeran; Humans; Ionizable lipid; Lipid nanoparticles; Liposomes - immunology; LNP; mRNA vaccine; mRNA Vaccines - immunology; Nanoparticles; Patisiran; Review; RNA, Small Interfering - immunology; SARS-CoV-2; Technology - methods; Tozinameran; Vaccines, Synthetic - immunology; COVID-19; SARS-CoV-2; Elasomeran; Tozinameran; Patisiran; Ionizable lipid; COVID-19 vaccine moderna; Lipid nanoparticles; LNP; mRNA vaccine
• ISSN: 1347-4367; 1880-0920; 1880-0920
• DOI: 10.1016/j.dmpk.2021.100424

Nucleic acid therapeutics are developing into precise medicines that can manipulate specific genes. However, the development of safe and effective delivery system for the target cells has remained a challenge. Lipid nanoparticles (LNPs) have provided a revolutionary delivery system that can ensure multiple clinical translation of RNA-based candidates. In 2018, Patisiran (Onpattro) was first approved as an LNP-based siRNA drug. In 2020, during the coronavirus disease 2019 (COVID-19) outbreak, LNPs have enabled the development of two SARS-CoV-2 mRNA vaccines, Tozinameran (Comirnaty or Pfizer-BioNTech COVID-19 vaccine) and Elasomeran (Spikevax or COVID-19 vaccine Moderna) for conditional approval. Here, we reviewed the state-of-the-art LNP technology employed in three approved drugs (one siRNA-based and two mRNA-based drugs) and discussed the differences in their mode of action, formulation design, and biodistribution.