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A comprehensive analysis of the use of nucleoside analogues in RNA therapeutics.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: A comprehensive analysis of the use of nucleoside analogues in RNA therapeutics.
Συγγραφείς: Kukushkina-Zvezdova AA; Sirius University of Science and Technology, 1 Olympic Avenue, Sirius Federal Territory, Sochi, 354340, Russia., Zherebtsova AA; Sirius University of Science and Technology, 1 Olympic Avenue, Sirius Federal Territory, Sochi, 354340, Russia., Telegina DV; Sirius University of Science and Technology, 1 Olympic Avenue, Sirius Federal Territory, Sochi, 354340, Russia., Skvortsov IA; Sirius University of Science and Technology, 1 Olympic Avenue, Sirius Federal Territory, Sochi, 354340, Russia., Ivanov RA; Sirius University of Science and Technology, 1 Olympic Avenue, Sirius Federal Territory, Sochi, 354340, Russia., Reshetnikov VV; Sirius University of Science and Technology, 1 Olympic Avenue, Sirius Federal Territory, Sochi, 354340, Russia. reshetnikov.vv@talantiuspeh.ru.
Πηγή: Journal of translational medicine [J Transl Med] 2026 Apr 07; Vol. 24 (1). Date of Electronic Publication: 2026 Apr 07.
Τύπος έκδοσης: Journal Article; Review; Research Support, Non-U.S. Gov't
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: BioMed Central Country of Publication: England NLM ID: 101190741 Publication Model: Electronic Cited Medium: Internet ISSN: 1479-5876 (Electronic) Linking ISSN: 14795876 NLM ISO Abbreviation: J Transl Med Subsets: MEDLINE
Imprint Name(s): Original Publication: [London] : BioMed Central, 2003-
Ιατρικοί όροι (MeSH): Nucleosides*/chemistry , Nucleosides*/therapeutic use , RNA*/therapeutic use , RNA*/chemistry, RNA, Messenger/therapeutic use ; RNA, Messenger/metabolism ; RNA, Messenger/genetics ; Humans ; Animals ; RNA Stability
Περίληψη: BACKGROUND: mRNA therapeutics represent a promising frontier in the development of vaccines, anti-cancer treatments, and gene replacement therapies. The mRNA platform facilitates the rapid design of effective and safe candidates. However, native mRNA molecules are inherently characterized by limited stability and high reactogenicity, which may compromise their in vivo efficacy. The incorporation of modified nucleoside analogues can address these challenges by extending the mRNA half-life and subsequently enhancing protein expression. MAIN BODY: Despite the discovery and widespread adoption of pseudouridine (Ψ) and N1-methylpseudouridine (m1Ψ) in mRNA therapeutics, these modifications have not fully addressed all inherent limitations of mRNA-based platforms. Consequently, identifying novel nucleoside analogues, their combinations, and alternative therapeutic strategies remains a critical area of research. This review provides a comprehensive overview of how commonly used nucleoside analogues influence mRNA stability, translation, and immunogenicity, while also discussing their natural distribution patterns in native mRNA. Furthermore, we examine experimental in vitro and in vivo data regarding the application of non-canonical nucleosides in cell and animal models and evaluate the future prospects of modified mRNA-based therapies. CONCLUSION: In conclusion, this review provides an extensive analysis of the properties of modified nucleosides employed in mRNA formulations and characterizes their impact on the overall efficacy of mRNA-based therapeutics in detail.
Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare that they have no conflict of interest.
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Grant Information: Agreement № 3-03 date February 18, 2025 «Sirius» Federal Territory
Contributed Indexing: Keywords: Nucleoside analogues; mRNA reactogenicity; mRNA stability; mRNA therapeutics
Substance Nomenclature: 0 (Nucleosides)
0 (RNA, Messenger)
63231-63-0 (RNA)
Entry Date(s): Date Created: 20260406 Date Completed: 20260628 Latest Revision: 20260829
Update Code: 20260829
PubMed Central ID: PMC13188432
DOI: 10.1186/s12967-026-08083-4
PMID: 41943009
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1479-5876
DOI:10.1186/s12967-026-08083-4