Vaccines on demand, part II: future reality
Abstract
INTRODUCTION: Prior to the emergence of SARS-CoV-2, the potential use of mRNA vaccines for a rapid pandemic response had been well described in the scientific literature, however during the SARS-CoV-2 outbreak we witnessed the large-scale deployment of the platform in a real pandemic setting. Of the three RNA platforms evaluated in clinical trials, including 1) conventional, non-amplifying mRNA (mRNA), 2) base-modified, non-amplifying mRNA (bmRNA), which incorporate chemically modified nucleotides, and 3) self-amplifying RNA (saRNA), the bmRNA technology emerged with superior clinical efficacy. AREAS COVERED: This review describes the current state of these mRNA vaccine technologies, evaluates their strengths and limitations, and argues that saRNA may have significant advantages if the limitations of stability and complexities of manufacturing can be overcome. EXPERT OPINION: The success of the SARS-CoV-2 mRNA vaccines has been remarkable. However, several challenges remain to be addressed before this technology can successfully be applied broadly to other disease targets. Innovation in the areas of mRNA engineering, novel delivery systems, antigen design, and high-quality manufacturing will be required to achieve the full potential of this disruptive technology.
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saRNAs use an RNA-dependent RNA polymerase from an alphavirus and conserved sequence elements at the 5′ and 3′ ends for replication, leading to robust and durable expression of encoded protein cargo.
“saRNAs use an RNA-dependent RNA polymerase from an alphavirus and the corresponding conserved sequence elements at the 5′ and 3′ ends for replication, leading to robust and durable expression of encoded protein cargo5–7.”
From Complete substitution with modified nucleotides in self-amplifying RNA suppresses the interferon response and increases potency (2025) · cites this paper as [6]
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“Unfortunately, the clinical reality thus far paints a less encouraging picture 6 , although the recent regulatory approval of a wild-type saRNA in Japan bodes well for the future of saRNA technologies 33,34 .”
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- Authors
- Geall, A. J., Kis, Z., & Ulmer, J. B.
- Affiliations
- Replicate Biosciences, San Diego, CA, USA
- Department of Chemical and Biological Engineering, The University of Sheffield, Sheffield, UK
- Immorna Biotherapeutics, Morrisville, North Carolina
- Corresponding author
- Ulmer, Jeffrey B.
- ORCID
- Geall, Andrew J.
- Venue
- Expert Opinion on Drug Discovery
- Publisher
- Informa UK Limited
- Published
- 2022-11-23
- Volume
- 18
- Issue
- 2
- Pages
- 119-127
- ISSN
- 1746-0441 (ISSN-L)
- 1746-045X
- OpenAlex
- W4309175814
- Cited by
- 10
- References
- 38
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 5 · 2023: 1
- FWCI
- 0.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Expert Opinion on Drug Discovery (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- mRNA vaccines, SARS-CoV-2, self-amplifying RNA, vaccine production, mRNA stability, mRNA delivery systems, antigen design, pandemic response
- MeSH terms
- COVID-19, SARS-CoV-2, Humans, RNA, RNA, Messenger, Vaccines, Vaccines, Synthetic
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