Self-amplifying RNA vaccines for infectious diseases
Open accessAbstract
Vaccinology is shifting toward synthetic RNA platforms which allow for rapid, scalable, and cell-free manufacturing of prophylactic and therapeutic vaccines. The simple development pipeline is based on in vitro transcription of antigen-encoding sequences or immunotherapies as synthetic RNA transcripts, which are then formulated for delivery. This approach may enable a quicker response to emerging disease outbreaks, as is evident from the swift pursuit of RNA vaccine candidates for the global SARS-CoV-2 pandemic. Both conventional and self-amplifying RNAs have shown protective immunization in preclinical studies against multiple infectious diseases including influenza, RSV, Rabies, Ebola, and HIV-1. Self-amplifying RNAs have shown enhanced antigen expression at lower doses compared to conventional mRNA, suggesting this technology may improve immunization. This review will explore how self-amplifying RNAs are emerging as important vaccine candidates for infectious diseases, the advantages of synthetic manufacturing approaches, and their potential for preventing and treating chronic infections.
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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 [7]
The Introduction’s Fig. 1 caption says alphavirus nsP1–4 proteins form an RNA-dependent RNA polymerase complex that recognizes 5′ and 3′ conserved sequence elements, amplifying vaccine-encoding transcripts and causing the encoded protein to accumulate. The Introduction also describes high-level antigen or therapeutic expression. These passages support robust expression, but they do not establish that protein expression is durable. (LLM, conf=0.86)
Experimental — accuracy not yet measuredsaRNA facilitates rapid candidate design and development, as well as cell-free molecule synthesis.
“Similar to other mRNA vaccine platforms, saRNA facilitates rapid candidate design and development, as well as cell-free molecule synthesis.152”
From COVID-19 mRNA vaccines: Platforms and current developments (2022) · cites this paper as [152]
The virus-derived polymerase amplifies mRNA transcripts intracellularly, enabling the expression of large amounts of antigen with reduced mRNA doses.
“The virus-derived polymerase amplifies mRNA transcripts intracellularly, enabling the expression of large amounts of antigen with reduced mRNA doses9.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [9]
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- Authors
- Bloom, K., van den Berg, F., & Arbuthnot, P.
- Affiliations
- South African Medical Research Council (ZA)
- Corresponding author
- Bloom, Kristie
- Venue
- Gene Therapy
- Published
- 2020-10-22
- Volume
- 28
- Issue
- 3-4
- Pages
- 117-129
- ISSN
- 0969-7128 (ISSN-L)
- 1476-5462
- PMC
- PMC7580817
- OpenAlex
- W3093949211
- Cited by
- 487
- References
- 136
- Citations by year
- 2026: 68 · 2025: 107 · 2024: 98 · 2023: 80 · 2022: 71 · 2021: 61 · 2020: 2
- FWCI
- 5.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Gene Therapy (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- South African Medical Research Council
- National Research Foundation (118022, 120383)
- Poliomyelitis Research Foundation (18/01)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- self-amplifying RNA vaccine, RNA vaccines, infectious disease vaccines, in vitro transcription, SARS-CoV-2, influenza, respiratory syncytial virus, rabies, Ebola, HIV-1, chronic infection
- MeSH terms
- COVID-19, SARS-CoV-2, COVID-19 Vaccines, Humans, RNA, Viral, Vaccination
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