Self-Amplifying RNA Approach for Protein Replacement Therapy
Open accessAbstract
Messenger RNA (mRNA) technology has already been successfully tested preclinically and there are ongoing clinical trials for protein replacement purposes; however, more effort has been put into the development of prevention strategies against infectious diseases. Apparently, mRNA vaccine approval against coronavirus disease 2019 (COVID-19) is a landmark for opening new opportunities for managing diverse health disorders based on this approach. Indeed, apart from infectious diseases, it has also been widely tested in numerous directions including cancer prevention and the treatment of inherited disorders. Interestingly, self-amplifying RNA (saRNA)-based technology is believed to display more developed RNA therapy compared with conventional mRNA technique in terms of its lower dosage requirements, relatively fewer side effects, and possessing long-lasting effects. Nevertheless, some challenges still exist that need to be overcome in order to achieve saRNA-based drug approval in clinics. Hence, the current review discusses the feasibility of saRNA utility for protein replacement therapy on various health disorders including rare hereditary diseases and also provides a detailed overview of saRNA advantages, its molecular structure, mechanism of action, and relevant delivery platforms.
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The current understanding of the field is that incorporating modified NTPs into saRNA abrogates downstream efficacy.
“However, the current understanding of the field is that incorporating modified NTPs into saRNA abrogates downstream efficacy, as reported by multiple independent groups5,19–28.”
From Complete substitution with modified nucleotides in self-amplifying RNA suppresses the interferon response and increases potency (2025) · cites this paper as [26]
Section 4 (page unavailable) says modified nucleosides are not a reasonable way to avoid innate immune recognition in saRNA because the modifications would vanish after the first round of amplification. It does not say that incorporating modified NTPs abrogates downstream efficacy, nor does it report that multiple independent groups found that outcome. (LLM, conf=0.86)
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- Authors
- Papukashvili, D., Rcheulishvili, N., Liu, C., Ji, Y., He, Y., & Wang, P. G.
- Affiliations
- Southern University of Science and Technology (CN)
- Corresponding author
- He, Yunjiao
- Wang, Peng George
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2022-10-25
- Volume
- 23
- Issue
- 21
- Pages
- 12884
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC9655356
- OpenAlex
- W4307631582
- Cited by
- 76
- References
- 129
- Citations by year
- 2026: 20 · 2025: 25 · 2024: 21 · 2023: 10
- FWCI
- 1.46
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Shenzhen Science and Technology Innovation Program (KQTD20200909113758004)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- self-amplifying RNA, protein replacement therapy, RNA therapeutics, rare hereditary disease, mechanism of action, mRNA vaccines, genetic disorders
- MeSH terms
- COVID-19, mRNA Vaccines, Humans, RNA, RNA, Messenger, Vaccines, Synthetic
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