Next-Generation mRNA Therapeutics: Self-Amplifying, Thermostable and Personalized mRNA Vaccines in the Era of Precision Medicine

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This is an unedited manuscript accepted for publication and provided as an Article in Press for early access at the author’s request. The article will undergo copyediting, typesetting, and galley proof review before final publication. Please be aware that errors may be identified during production that could affect the content. All legal disclaimers of the journal apply.

Year : 2025 | Volume : 2 | 02 | Page :
    By

    Kapadiya Kris Prakashchandra,

  1. Student, GTU School of Pharmacy, Gandhinagar-382028- Gujarat, India

Abstract

Messenger RNA (mRNA) technology has brought a major change in modern medicine, especially after its successful use in COVID-19 vaccines. However, early mRNA vaccines faced several problems such as low stability, strict cold storage requirements, and lack of personalized treatment. To overcome these challenges, next-generation mRNA technologies have been developed, including self-amplifying mRNA (saRNA), thermostable mRNA vaccines, and personalized mRNA vaccines. This article discusses the development of mRNA therapeutics, the limitations of first-generation mRNA vaccines, and recent progress in advanced mRNA systems. The structure, working mechanism, benefits, and uses of saRNA are explained. The importance of thermostable mRNA vaccines and the methods used to improve their heat stability are also described along with their benefits for global health. The concept of personalized mRNA vaccines, especially for cancer treatment and precision oncology, is highlighted. In addition, different delivery systems such as lipid nanoparticles, polymer-based carriers, and targeted delivery methods are included. The role of artificial intelligence in mRNA design, applications beyond COVID-19, safety, regulatory aspects, and future possibilities of mRNA therapeutics are also discussed. This article aims to give a clear and updated understanding of next-generation mRNA therapeutics.

Keywords: 1. mRNA therapeutics 2. Self-amplifying mRNA 3. Thermostable mRNA vaccines 4. Personalized cancer vaccines 5. Precision medicine

How to cite this article:
Kapadiya Kris Prakashchandra. Next-Generation mRNA Therapeutics: Self-Amplifying, Thermostable and Personalized mRNA Vaccines in the Era of Precision Medicine. International Journal of Vaccines. 2025; 02(02):-.
How to cite this URL:
Kapadiya Kris Prakashchandra. Next-Generation mRNA Therapeutics: Self-Amplifying, Thermostable and Personalized mRNA Vaccines in the Era of Precision Medicine. International Journal of Vaccines. 2025; 02(02):-. Available from: https://journals.stmjournals.com/ijv/article=2025/view=234793


References

  • Pardi N, Hogan MJ, Porter FW, Weissman D. mRNA vaccines—A new era in vaccinology. Nat Rev Drug Discov. 2018;17(4):261–279.
  • Sahin U, Karikó K, Türeci Ö. mRNA-based therapeutics—Developing a new class of drugs. Nat Rev Drug Discov. 2014;13(10):759–780.
  • Karikó K, Muramatsu H, Welsh FA, Ludwig J, Kato H, Akira S, et al. Incorporation of pseudouridine into mRNA yields superior non-immunogenic vector. Immunity. 2008;28(2):165–175.
  • Weissman D. mRNA transcript therapy. Expert Rev Vaccines. 2015;14(2):265–281.
  • Blakney AK, Ip S, Geall AJ. An update on self-amplifying mRNA vaccine development. Vaccines (Basel). 2021;9(2):97.
  • Vogel AB, Lambert L, Kinnear E, Buska S, Erbar S, Reuter KC, et al. Self-amplifying RNA vaccines give equivalent protection against influenza to mRNA vaccines but at much lower doses. Mol Ther. 2018;26(2):446–455.
  • McKay PF, Hu K, Blakney AK, Samnuan K, Brown JC, Penn R, et al. Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine. Nat Commun. 2020;11:3523.
  • Beissert T, Perkovic M, Vogel A, Erbar S, Walzer KC, Hempel T, et al. A trans-amplifying RNA vaccine strategy for induction of potent immune responses. Mol Ther. 2020;28(1):119–128.
  • Lundstrom K. Self-amplifying RNA viruses as RNA vaccines. Int J Mol Sci. 2020;21(14):513.
  • Crommelin DJA, Anchordoquy TJ, Volkin DB, Jiskoot W, Mastrobattista E. Addressing the cold reality of mRNA vaccine stability. J Pharm Sci. 2021;110(3):997–1001.
  • Zhang NN, Li XF, Deng YQ, Zhao H, Huang YJ, Yang G, et al. A thermostable mRNA vaccine against COVID-19. Cell. 2020;182(5):1271–1283.
  • Ma Y, Guo Y, Wang X, Li Q, Deng Y, Liu J. Lyophilized lipid nanoparticle-based mRNA vaccine with improved thermostability. Pharmaceutics. 2022;14(1):182.
  • Verbeke R, Lentacker I, De Smedt SC, Dewitte H. Three decades of messenger RNA vaccine development. Nano Today. 2019;28:100766.
  • Kis Z, Kontoravdi C, Shattock R, Shah N. Resources, production scales and time required for producing RNA vaccines. Vaccines (Basel). 2021;9(1):3.
  • Sahin U, Derhovanessian E, Miller M, Kloke BP, Simon P, Löwer M, et al. Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature. 2017;547(7662):222–226.
  • Ott PA, Hu Z, Keskin DB, Shukla SA, Sun J, Bozym DJ, et al. An immunogenic personal neoantigen vaccine for patients with melanoma. Nature. 2017;547(7662):217–221.
  • Ribas A, Dummer R, Puzanov I, VanderWalde A, Andtbacka RHI, Michielin O, et al. Oncolytic virotherapy promotes intratumoral T-cell infiltration and improves anti-PD-1 immunotherapy. Cell. 2017;170(6):1109–1119.
  • Vormehr M, Türeci Ö, Sahin U. Harnessing the power of RNA vaccines in cancer. Nat Rev Cancer. 2022;22(6):373–385.
  • Kreiter S, Vormehr M, van de Roemer N, Diken M, Löwer M, Diekmann J, et al. Mutant MHC class II epitopes drive therapeutic immune responses to cancer. Nature. 2015;520(7549):692–696.
  • Hou X, Zaks T, Langer R, Dong Y. Lipid nanoparticles for mRNA delivery. Nat Rev Mater. 2021;6(12):1078–1094.
  • Shi Y, Liu X, Zhang Q, Wang L, Meng Q. Progress and prospects of mRNA-based drugs in preclinical and clinical development. Signal Transduct Target Ther. 2024;9:112.
  • Lu RM, Hwang YC, Liu IJ, Lee CC, Tsai HZ, Li HJ, et al. Current landscape of mRNA technologies and delivery systems. J Biomed Sci. 2024;31:48.
  • Casmil IC, Blakney AK, Geall AJ. The advent of clinical self-amplifying RNA vaccines. Mol Ther Nucleic Acids. 2025;30:102–118.
  • Vallet T, Borcard L, Aucouturier J, Gerdts V, Mutwiri G. Self-amplifying RNA: Advantages and challenges of a next-generation vaccine platform. Vaccines (Basel). 2025;13(2):214.
  • Li X, Zhang Y, He S, Li Y, Wang J. Design strategies for novel lipid nanoparticles for mRNA therapeutics. Pharmaceutics. 2025;17(3):356.
  • Al Fayez N, Alothman M, Alqahtani AS. Recent advancement in mRNA vaccine development and perspective on future strategies. Front Immunol. 2023;14:1198432.
  • Laila UE, Yasmin T, Muneer A, Hameed F, Shahzad M. Emerging prospects of mRNA cancer vaccines. Front Immunol. 2024;15:1448489.
  • Ramadan E, Sabry R, Abdallah O, El-Sayed I. Advances in mRNA lipid nanoparticle-based cancer vaccines. J Pers Med. 2024;14(10):1092.
  • Han J, Kim B, Shin K, Lee K, Park S. Lipid nanoparticle-based mRNA delivery systems for cancer immunotherapy. Nanoconvergence. 2023;10:41.
  • Jiang Z, He Z, Xu J, Chen Y, Liu X. Emerging advances in delivery systems for mRNA cancer vaccines. J Control Release. 2024;367:173–189.
  • Huang S. mRNA vaccines as cancer therapies. Chin Med J (Engl). 2024;137(23):2801–2810.
  • Leong KY, Wan Sulaiman WS, Tye GJ. A comprehensive review of mRNA vaccine technology and future perspectives. Virol J. 2025;22:31.
  • Zhang Y, Liu J, Wang T, He Q. Current progress and future perspectives of RNA-based cancer vaccines: A 2025 update. Biomark Res. 2025;13:19.
  • Zhao M, Li H, Wang Y, Zhang L. Lipid nanoparticle-assisted mRNA therapy for cancer. AIP Adv. 2025;12:031328.
  • Seo SH, Kim H, Lee J, Park Y. Advancements and challenges in next-generation mRNA manufacturing and delivery. Clin Exp Vaccine Res. 2025;14:e40.
  • Xu X, Li Q, Zhang Y, Wang J, Zhu L. Recent advances in site-specific lipid nanoparticles for nucleic acid delivery. ACS Nano. 2023;17(16):15812–15829.
  • CAS Editorial Team. The future of mRNA vaccines beyond COVID-19. CAS Insights. 2025.
  • Wang Y, Zhang H, Chen Z, Li X. Recent advances in lipid nanoparticles and programmable vaccines. Small. 2025;21:e2506812.
  • Zhang H, Liu K, Li J, Zhu X, Chen J. Algorithm for optimized mRNA design improves stability and immunogenicity. arXiv. 2020;arXiv:2004.10177.
Ahead of Print Subscription Review Article
Volume 02
02
Received 04/12/2025
Accepted 05/12/2025
Published 26/12/2025
Publication Time 22 Days
104

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