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Nanotechnology-based mRNA vaccines

Nature Reviews Methods Primers volume 3, Article number: 63 (2023) Cite this article

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Abstract

mRNA vaccines have emerged as a revolutionary tool to generate rapid and precise immune responses against infectious diseases and cancers. Compared with conventional vaccines such as inactivated viruses, viral vectors, protein subunits or DNA-based vaccines, mRNA vaccines stand out owing to multiple advantages, including simplicity of design, fast production, enhanced safety and high efficacy. Nevertheless, efficient and targeted delivery of mRNA molecules remains a significant challenge owing to their inherent instability and susceptibility to degradation. Nanotechnology offers innovative solutions to surmount these obstacles and amplify the potency of mRNA vaccines. This Primer aims to outline a modular approach to developing biomaterials and nanotechnology for mRNA vaccines, with a focus on particle design, formulation evaluation and therapeutic applications. We delve into the underlying mechanisms of nanoparticle-facilitated mRNA protection, cellular uptake, endosomal escape and immune stimulation. We underscore the critical parameters that impact the manufacturing and clinical implementation of nanomaterial-based mRNA vaccines. Finally, we present the current limitations and future perspectives in the advancement of nanotechnology-enhanced mRNA vaccines for broad applications in prophylactic and therapeutic interventions.

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Fig. 1: Classification and mechanism of mRNA vaccines.
Fig. 2: Experimental workflow of nanotechnology-based mRNA vaccines.
Fig. 3: Characterization and toxicity of mRNA delivery nanoplatforms and mRNA vaccine.
Fig. 4: Structural characterization of COVID-19 mRNA vaccines and the mechanisms of mRNA vaccines against infectious diseases.
Fig. 5: The mechanisms of mRNA cancer vaccines.

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Acknowledgements

The authors acknowledge the support from the American Heart Association (AHA) Transformational Project Award (23TPA1072337; W.T.), AHA’s Second Century Early Faculty Independence Award (23SCEFIA1151841; W.T.), American Lung Association (ALA) Cancer Discovery Award (LCD1034625; W.T.), ALA Courtney Cox Cole Lung Cancer Research Award (No. 2022A017206; W.T.), Novo Nordisk ValidatioNN Award (No. 2023A009607; W.T.), Harvard/Brigham Health & Technology Innovation Fund (No. 2023A004452; W.T.), Department of Anesthesiology-Basic Scientist Grant (No. 2420 BPA075; W.T.), Nanotechnology Foundation (No. 2022A002721; W.T.), Gillian Reny Stepping Strong Center for Trauma Innovation Breakthrough Innovator Award (No. 113548; W.T.), Khoury Innovation Award (No. 2020A003219; W.T.), Center for Nanomedicine Research Fund (No. 2019A014810; W.T.), National Institute of Allergy and Infectious Diseases (No. R01AI174902; Y.D.), National Institute of General Medical Sciences (No. R35GM144117; Y.D.), the National Institutes of Health (R01 EB025192-01A1 and R01 CA269787-01; D.J.S.) and Farokhzad Family Distinguished Chair Foundation (No. 018129; W.T.).

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Author notes

  1. These authors contributed equally: Shuying Chen, Xiangang Huang, Yonger Xue, Ester Álvarez-Benedicto.

Authors and Affiliations

  1. Center for Nanomedicine and Department of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Shuying Chen, Xiangang Huang, Yesi Shi, Wei Chen, Seyoung Koo & Wei Tao

  2. Icahn Genomics Institute, Precision Immunology Institute, Department of Oncological Sciences, Tisch Cancer Institute, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Yonger Xue & Yizhou Dong

  3. Division of Pharmaceutics and Pharmacology, College of Pharmacy, Ohio State University, Columbus, OH, USA

    Yonger Xue & Yizhou Dong

  4. Department of Biochemistry, Department of Biomedical Engineering, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA

    Ester Álvarez-Benedicto & Daniel J. Siegwart

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  1. Shuying Chen
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Contributions

Introduction (S.C., X.H., Y.X. and E.Á.-B.); Experimentation (S.C., X.H., Y.X. and E.Á.-B.); Results (S.C., X.H. and Y.X.); Applications (S.C., X.H., Y.X. and E.Á.-B.); Reproducibility and data deposition (S.C. and E.Á.-B.); Limitations and optimizations (S.C., X.H., Y.X., Y.S., W.C. and S.K.); Outlook (S.C., X.H., E.Á.-B. and W.C.); and overview of the Primer (D.J.S., Y.D. and W.T.).

Corresponding authors

Correspondence to Daniel J. Siegwart, Yizhou Dong or Wei Tao.

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Competing interests

D.J.S. declares the following competing interests: ReCode Therapeutics, Tome Biosciences, Signify Bio, and Pfizer Inc. Y.D. is a scientific advisory board member of Oncorus Inc., Arbor Biotechnologies, and FL85. The other authors declare no competing interests.

Peer review

Peer review information

Nature Reviews Methods Primers thanks Anna Blakney, Dan Peer, Joseph Rosenecker and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Glossary

Clearance rate

The volume or quantity of a substance removed from a system per unit of time.

Encapsulation efficiency

The proportion of mRNA molecules successfully enclosed within the nanoparticle carrier.

Self-amplifying mRNA vaccines

mRNA vaccines incorporate engineered mRNA sequences to perpetually generate specific antigens, thereby augmenting and extending the immune response.

Zeta potential

The electrokinetic potential difference between the dispersing medium and the immobile layer of fluid adhered to the dispersed particle, reflecting the surface charge and potential interactions.

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Chen, S., Huang, X., Xue, Y. et al. Nanotechnology-based mRNA vaccines. Nat Rev Methods Primers 3, 63 (2023). https://doi.org/10.1038/s43586-023-00246-7

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