Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
권호 표지
DOI QR코드

DOI QR Code

Development of mRNA Vaccines/Therapeutics and Their Delivery System

  • Sora Son (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University) ;
  • Kyuri Lee (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University)
  • Received : 2022.10.31
  • Accepted : 2022.12.18
  • Published : 2023.01.31
Download PDF
⟨ Previous Next ⟩

Abstract

The rapid development of mRNA vaccines has contributed to the management of the current coronavirus disease 2019 (COVID-19) pandemic, suggesting that this technology may be used to manage future outbreaks of infectious diseases. Because the antigens targeted by mRNA vaccines can be easily altered by simply changing the sequence present in the coding region of mRNA structures, it is more appropriate to develop vaccines, especially during rapidly developing outbreaks of infectious diseases. In addition to allowing rapid development, mRNA vaccines have great potential in inducing successful antigen-specific immunity by expressing target antigens in cells and simultaneously triggering immune responses. Indeed, the two COVID-19 mRNA vaccines approved by the U.S. Food and Drug Administration have shown significant efficacy in preventing infections. The ability of mRNAs to produce target proteins that are defective in specific diseases has enabled the development of options to treat intractable diseases. Clinical applications of mRNA vaccines/therapeutics require strategies to safely deliver the RNA molecules into targeted cells. The present review summarizes current knowledge about mRNA vaccines/ therapeutics, their clinical applications, and their delivery strategies.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea (NRF), funded by the Ministry of Science & ICT (Basic Science Research Program (2020R1C1C1007820) and the Bio & Medical Technology Development Program (2022M3E5F1017743), and by a grant (22203MFDS402, 22203MFDS405) from the Ministry of Food and Drug Safety in 2022.

References

  1. Berraondo, P., Martini, P.G.V., Avila, M.A., and Fontanellas, A. (2019). Messenger RNA therapy for rare genetic metabolic diseases. Gut 68, 1323-1330. https://doi.org/10.1136/gutjnl-2019-318269
  2. Billingsley, M.M., Singh, N., Ravikumar, P., Zhang, R., June, C.H., and Mitchell, M.J. (2020). Ionizable lipid nanoparticle-mediated mRNA delivery for human CAR T cell engineering. Nano Lett. 20, 1578-1589. https://doi.org/10.1021/acs.nanolett.9b04246
  3. Byun, M.J., Lim, J., Kim, S.N., Park, D.H., Kim, T.H., Park, W., and Park, C.G. (2022). Advances in nanoparticles for effective delivery of RNA therapeutics. Biochip J. 16, 128-145. https://doi.org/10.1007/s13206-022-00052-5
  4. Cheng, Q., Wei, T., Farbiak, L., Johnson, L.T., Dilliard, S.A., and Siegwart, D.J. (2020). Selective organ targeting (SORT) nanoparticles for tissue-specific mRNA delivery and CRISPR-Cas gene editing. Nat. Nanotechnol. 15, 313-320. https://doi.org/10.1038/s41565-020-0669-6
  5. Hou, X., Zaks, T., Langer, R., and Dong, Y. (2021). Lipid nanoparticles for mRNA delivery. Nat. Rev. Mater. 6, 1078-1094. https://doi.org/10.1038/s41578-021-00358-0
  6. Jackson, N.A.C., Kester, K.E., Casimiro, D., Gurunathan, S., and DeRosa, F. (2020). The promise of mRNA vaccines: a biotech and industrial perspective. NPJ Vaccines 5, 11.
  7. Kariko, K., Buckstein, M., Ni, H., and Weissman, D. (2005). Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA. Immunity 23, 165-175. https://doi.org/10.1016/j.immuni.2005.06.008
  8. Kariko, K., Muramatsu, H., Keller, J.M., and Weissman, D. (2012). Increased erythropoiesis in mice injected with submicrogram quantities of pseudouridine-containing mRNA encoding erythropoietin. Mol. Ther. 20, 948-953. https://doi.org/10.1038/mt.2012.7
  9. Kariko, K., Muramatsu, H., Welsh, F.A., Ludwig, J., Kato, H., Akira, S., and Weissman, D. (2008). Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Mol. Ther. 16, 1833-1840. https://doi.org/10.1038/mt.2008.200
  10. Kwon, H., Kim, M., Seo, Y., Moon, Y.S., Lee, H.J., Lee, K., and Lee, H. (2018). Emergence of synthetic mRNA: in vitro synthesis of mRNA and its applications in regenerative medicine. Biomaterials 156, 172-193. https://doi.org/10.1016/j.biomaterials.2017.11.034
  11. Lee, K., Kim, M., Seo, Y., and Lee, H. (2018). Development of mRNA vaccines and their prophylactic and therapeutic applications. Nano Res. 11, 5173-5192. https://doi.org/10.1007/s12274-018-2095-8
  12. Magadum, A., Kaur, K., and Zangi, L. (2019). mRNA-based protein replacement therapy for the heart. Mol. Ther. 27, 785-793. https://doi.org/10.1016/j.ymthe.2018.11.018
  13. Pardi, N., Hogan, M.J., Porter, F.W., and Weissman, D. (2018). mRNA vaccines - a new era in vaccinology. Nat. Rev. Drug Discov. 17, 261-279. https://doi.org/10.1038/nrd.2017.243
  14. Paunovska, K., Loughrey, D., and Dahlman, J.E. (2022). Drug delivery systems for RNA therapeutics. Nat. Rev. Genet. 23, 265-280. https://doi.org/10.1038/s41576-021-00439-4
  15. Sahin, U., Kariko, K., and Tureci, O. (2014). mRNA-based therapeutics--developing a new class of drugs. Nat. Rev. Drug Discov. 13, 759-780. https://doi.org/10.1038/nrd4278
  16. Schlee, M. and Hartmann, G. (2016). Discriminating self from non-self in nucleic acid sensing. Nat. Rev. Immunol. 16, 566-580. https://doi.org/10.1038/nri.2016.78
  17. Sebastiani, F., Yanez Arteta, M., Lerche, M., Porcar, L., Lang, C., Bragg, R.A., Elmore, C.S., Krishnamurthy, V.R., Russell, R.A., Darwish, T., et al. (2021). Apolipoprotein E binding drives structural and compositional rearrangement of mRNA-containing lipid nanoparticles. ACS Nano 15, 6709-6722. https://doi.org/10.1021/acsnano.0c10064
  18. Uchida, S., Itaka, K., Uchida, H., Hayakawa, K., Ogata, T., Ishii, T., Fukushima, S., Osada, K., and Kataoka, K. (2013). In vivo messenger RNA introduction into the central nervous system using polyplex nanomicelle. PLoS One 8, e56220.
  19. Vallazza, B., Petri, S., Poleganov, M.A., Eberle, F., Kuhn, A.N., and Sahin, U. (2015). Recombinant messenger RNA technology and its application in cancer immunotherapy, transcript replacement therapies, pluripotent stem cell induction, and beyond. Wiley Interdiscip. Rev. RNA 6, 471-499. https://doi.org/10.1002/wrna.1288
  20. Wang, F., Zuroske, T., and Watts, J.K. (2020). RNA therapeutics on the rise. Nat. Rev. Drug Discov. 19, 441-442. https://doi.org/10.1038/d41573-020-00078-0
  21. Warren, L. and Lin, C. (2019). mRNA-based genetic reprogramming. Mol. Ther. 27, 729-734. https://doi.org/10.1016/j.ymthe.2018.12.009
  22. Yoon, B.K., Oh, T.G., Bu, S., Seo, K.J., Kwon, S.H., Lee, J.Y., Kim, Y., Kim, J.W., Ahn, H.S., and Fang, S. (2022). The peripheral immune landscape in a patient with myocarditis after the administration of BNT162b2 mRNA vaccine. Mol. Cells 45, 738-748. https://doi.org/10.14348/molcells.2022.0031
  23. Zelphati, O., Nguyen, C., Ferrari, M., Felgner, J., Tsai, Y., and Felgner, P.L. (1998). Stable and monodisperse lipoplex formulations for gene delivery. Gene Ther. 5, 1272-1282. https://doi.org/10.1038/sj.gt.3300707