The Clinical Progress of MRNA Vaccines and Immunotherapies

Overview

Journal Nat Biotechnol

Specialty Biotechnology

Date 2022 May 9

PMID 35534554

Authors

Ann J Barbier

Allen Yujie Jiang

Peng Zhang

Richard Wooster

Daniel G Anderson

Affiliations

Soon will be listed here.

Abstract

The emergency use authorizations (EUAs) of two mRNA-based severe acute respiratory syndrome coronavirus (SARS-CoV)-2 vaccines approximately 11 months after publication of the viral sequence highlights the transformative potential of this nucleic acid technology. Most clinical applications of mRNA to date have focused on vaccines for infectious disease and cancer for which low doses, low protein expression and local delivery can be effective because of the inherent immunostimulatory properties of some mRNA species and formulations. In addition, work on mRNA-encoded protein or cellular immunotherapies has also begun, for which minimal immune stimulation, high protein expression in target cells and tissues, and the need for repeated administration have led to additional manufacturing and formulation challenges for clinical translation. Building on this momentum, the past year has seen clinical progress with second-generation coronavirus disease 2019 (COVID-19) vaccines, Omicron-specific boosters and vaccines against seasonal influenza, Epstein-Barr virus, human immunodeficiency virus (HIV) and cancer. Here we review the clinical progress of mRNA therapy as well as provide an overview and future outlook of the transformative technology behind these mRNA-based drugs.

Citing Articles

LNP-RNA-mediated antigen presentation leverages SARS-CoV-2-specific immunity for cancer treatment.

Xue Y, Hou X, Zhong Y, Zhang Y, Du S, Kang D Nat Commun. 2025; 16(1):2198.

PMID: 40038251 PMC: 11880362. DOI: 10.1038/s41467-025-57149-2.

Machine learning-assisted design of immunomodulatory lipid nanoparticles for delivery of mRNA to repolarize hyperactivated microglia.

Rafiei M, Shojaei A, Chau Y Drug Deliv. 2025; 32(1):2465909.

PMID: 40028722 PMC: 11878168. DOI: 10.1080/10717544.2025.2465909.

production of engineered ACE2 decoy protects lungs from SARS-CoV-2 infection.

Suzuki Y, Miyazaki T, Ida Y, Suzuki T, Itoh Y, Nakao S Mol Ther Nucleic Acids. 2025; 36(1):102467.

PMID: 40027884 PMC: 11869860. DOI: 10.1016/j.omtn.2025.102467.

Landscape of Noncoding RNA in the Hypoxic Tumor Microenvironment.

Gong L, Zou C, Zhang H, Yang F, Qi G, Ma Z Genes (Basel). 2025; 16(2).

PMID: 40004471 PMC: 11855738. DOI: 10.3390/genes16020140.

Targeting Enterotoxins: Advancing Vaccine Development for Enterotoxigenic ETEC.

Salvador-Erro J, Pastor Y, Gamazo C Toxins (Basel). 2025; 17(2).

PMID: 39998088 PMC: 11860656. DOI: 10.3390/toxins17020071.

References

Corbett K, Edwards D, Leist S, Abiona O, Boyoglu-Barnum S, Gillespie R . SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness. Nature. 2020; 586(7830):567-571. PMC: 7581537. DOI: 10.1038/s41586-020-2622-0. View

Wolff J, Malone R, Williams P, Chong W, Acsadi G, Jani A . Direct gene transfer into mouse muscle in vivo. Science. 1990; 247(4949 Pt 1):1465-8. DOI: 10.1126/science.1690918. View

Kutzler M, Weiner D . DNA vaccines: ready for prime time?. Nat Rev Genet. 2008; 9(10):776-88. PMC: 4317294. DOI: 10.1038/nrg2432. View

Van Hoecke L, Roose K . How mRNA therapeutics are entering the monoclonal antibody field. J Transl Med. 2019; 17(1):54. PMC: 6387507. DOI: 10.1186/s12967-019-1804-8. View

Maruggi G, Zhang C, Li J, Ulmer J, Yu D . mRNA as a Transformative Technology for Vaccine Development to Control Infectious Diseases. Mol Ther. 2019; 27(4):757-772. PMC: 6453507. DOI: 10.1016/j.ymthe.2019.01.020. View

Schlake T, Thess A, Thran M, Jordan I . mRNA as novel technology for passive immunotherapy. Cell Mol Life Sci. 2018; 76(2):301-328. PMC: 6339677. DOI: 10.1007/s00018-018-2935-4. View

Jackson N, Kester K, Casimiro D, Gurunathan S, DeRosa F . The promise of mRNA vaccines: a biotech and industrial perspective. NPJ Vaccines. 2020; 5:11. PMC: 7000814. DOI: 10.1038/s41541-020-0159-8. View

Kowalski P, Rudra A, Miao L, Anderson D . Delivering the Messenger: Advances in Technologies for Therapeutic mRNA Delivery. Mol Ther. 2019; 27(4):710-728. PMC: 6453548. DOI: 10.1016/j.ymthe.2019.02.012. View

Colella P, Ronzitti G, Mingozzi F . Emerging Issues in AAV-Mediated Gene Therapy. Mol Ther Methods Clin Dev. 2018; 8:87-104. PMC: 5758940. DOI: 10.1016/j.omtm.2017.11.007. View

10.

Sabnis S, Kumarasinghe E, Salerno T, Mihai C, Ketova T, Senn J . A Novel Amino Lipid Series for mRNA Delivery: Improved Endosomal Escape and Sustained Pharmacology and Safety in Non-human Primates. Mol Ther. 2018; 26(6):1509-1519. PMC: 5986714. DOI: 10.1016/j.ymthe.2018.03.010. View

11.

Chahal J, Khan O, Cooper C, McPartlan J, Tsosie J, Tilley L . Dendrimer-RNA nanoparticles generate protective immunity against lethal Ebola, H1N1 influenza, and Toxoplasma gondii challenges with a single dose. Proc Natl Acad Sci U S A. 2016; 113(29):E4133-42. PMC: 4961123. DOI: 10.1073/pnas.1600299113. View

12.

Besin G, Milton J, Sabnis S, Howell R, Mihai C, Burke K . Accelerated Blood Clearance of Lipid Nanoparticles Entails a Biphasic Humoral Response of B-1 Followed by B-2 Lymphocytes to Distinct Antigenic Moieties. Immunohorizons. 2019; 3(7):282-293. DOI: 10.4049/immunohorizons.1900029. View

13.

Sahin U, Oehm P, Derhovanessian E, Jabulowsky R, Vormehr M, Gold M . An RNA vaccine drives immunity in checkpoint-inhibitor-treated melanoma. Nature. 2020; 585(7823):107-112. DOI: 10.1038/s41586-020-2537-9. View

14.

Adams D, Gonzalez-Duarte A, ORiordan W, Yang C, Ueda M, Kristen A . Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis. N Engl J Med. 2018; 379(1):11-21. DOI: 10.1056/NEJMoa1716153. View

15.

Kariko K, Muramatsu H, Welsh F, Ludwig J, Kato H, Akira S . Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Mol Ther. 2008; 16(11):1833-40. PMC: 2775451. DOI: 10.1038/mt.2008.200. View

16.

Thess A, Grund S, Mui B, Hope M, Baumhof P, Fotin-Mleczek M . Sequence-engineered mRNA Without Chemical Nucleoside Modifications Enables an Effective Protein Therapy in Large Animals. Mol Ther. 2015; 23(9):1456-64. PMC: 4817881. DOI: 10.1038/mt.2015.103. View

17.

Guan S, Rosenecker J . Nanotechnologies in delivery of mRNA therapeutics using nonviral vector-based delivery systems. Gene Ther. 2017; 24(3):133-143. DOI: 10.1038/gt.2017.5. View

18.

Kauffman K, Webber M, Anderson D . Materials for non-viral intracellular delivery of messenger RNA therapeutics. J Control Release. 2016; 240:227-234. DOI: 10.1016/j.jconrel.2015.12.032. View

19.

Pardi N, Hogan M, Porter F, Weissman D . mRNA vaccines - a new era in vaccinology. Nat Rev Drug Discov. 2018; 17(4):261-279. PMC: 5906799. DOI: 10.1038/nrd.2017.243. View

20.

Sahin U, Kariko K, Tureci O . mRNA-based therapeutics--developing a new class of drugs. Nat Rev Drug Discov. 2014; 13(10):759-80. DOI: 10.1038/nrd4278. View