Recent advances in mRNA vaccine technology
Section snippets
Introduction: overcoming early challenges for RNA vaccines
The concept of genetic (DNA and RNA) vaccines was raised decades ago with the hope that a flexible, easy-to-produce, safe and effective vaccine class could be generated. Until the late 2000s, the emphasis was on the development of DNA-based approaches [1] due to the hurdles stemming from RNA’s instability, inefficient in vivo delivery, and its stimulation of excessive inflammatory responses. Producing in vitro-transcribed (IVT) messenger RNA (mRNA) is a fairly straightforward process [2,3], but
Recent innovations
The most important innovations in mRNA vaccine technology in recent years have been in the areas of: 1) engineering of mRNA sequences, 2) development of methods that enable simple, rapid and large-scale cGMP production of mRNA; and 3) development of highly efficient and safe mRNA vaccine delivery materials.
Future directions and outstanding questions regarding mRNA vaccines
While the past several years have witnessed a rapid pace of innovation in mRNA manufacturing, in vivo delivery, and immunogenicity, there remains much room for improvement and investigation. Here, we briefly highlight three interrelated topics that, if better understood, could propel the field further: (1) differences in mRNA preparation, (2) differences between animal models and humans, and (3) mechanisms of immunogenicity of mRNA vaccines.
Conclusions
The past several years yielded critically important advancements in the field of mRNA vaccines and provided evidence for the viability of this novel vaccine modality. New manufacturing methods and delivery materials will facilitate the rapid, inexpensive mass production of next-generation mRNA vaccines. Data from human trials for both cancer and infectious disease mRNA vaccines are encouraging, but further improvements of the delivery materials and a more complete understanding of the
Conflict of interest statement
In accordance with the University of Pennsylvania policies and procedures and our ethical obligations as researchers, we report that Drew Weissman is named on patents that describe the use of nucleoside-modified mRNA as a platform to deliver therapeutic proteins. Drew Weissman and Norbert Pardi are also named on a patent describing the use of modified mRNA in lipid nanoparticles as a vaccine platform. We have disclosed those interests fully to the University of Pennsylvania, and we have in
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgements
N.P. was supported by the National Institute of Allergy and Infectious Diseases (1R01AI146101). D.W. was supported by the National Institute of Allergy and Infectious Diseases (R01-AI050484, R01-AI124429 and R01-AI084860). M.J.H. is a Cancer Research Institute Irvington Fellow supported by the Cancer Research Institute. The authors apologize to all colleagues whose great studies could not be cited here owing to space limitations.
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