A novel deep generative model for mRNA vaccine development : Designing 5′ UTRs with N1-methyl-pseudouridine modification
Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review
Author(s)
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Detail(s)
Original language | English |
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Pages (from-to) | 1814-1826 |
Number of pages | 13 |
Journal / Publication | Acta Pharmaceutica Sinica B |
Volume | 14 |
Issue number | 4 |
Online published | 5 Nov 2023 |
Publication status | Published - Apr 2024 |
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DOI | DOI |
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Link to Scopus | https://www.scopus.com/record/display.uri?eid=2-s2.0-85183550374&origin=recordpage |
Permanent Link | https://scholars.cityu.edu.hk/en/publications/publication(36f4aed7-0cee-48ab-b520-f2885b138552).html |
Abstract
Efficient translation mediated by the 5′ untranslated region (5′ UTR) is essential for the robust efficacy of mRNA vaccines. However, the N1-methyl-pseudouridine (m1Ψ) modification of mRNA can impact the translation efficiency of the 5′ UTR. We discovered that the optimal 5′ UTR for m1Ψ-modified mRNA (m1Ψ–5′ UTR) differs significantly from its unmodified counterpart, highlighting the need for a specialized tool for designing m1Ψ–5′ UTRs rather than directly utilizing high-expression endogenous gene 5′ UTRs. In response, we developed a novel machine learning-based tool, Smart5UTR, which employs a deep generative model to identify superior m1Ψ–5′ UTRs in silico. The tailored loss function and network architecture enable Smart5UTR to overcome limitations inherent in existing models. As a result, Smart5UTR can successfully design superior 5′ UTRs, greatly benefiting mRNA vaccine development. Notably, Smart5UTR-designed superior 5′ UTRs significantly enhanced antibody titers induced by COVID-19 mRNA vaccines against the Delta and Omicron variants of SARS-CoV-2, surpassing the performance of vaccines using high-expression endogenous gene 5′ UTRs. © 2024 The Authors.
Research Area(s)
- mRNAvaccine, Machine learning, 50 UTR, mRNA design, Sequence design, N1-methyl-pseudouridine, COVID-19, SARS-CoV-2
Citation Format(s)
A novel deep generative model for mRNA vaccine development: Designing 5′ UTRs with N1-methyl-pseudouridine modification. / Tang, Xiaoshan; Huo, Miaozhe; Chen, Yuting et al.
In: Acta Pharmaceutica Sinica B, Vol. 14, No. 4, 04.2024, p. 1814-1826.
In: Acta Pharmaceutica Sinica B, Vol. 14, No. 4, 04.2024, p. 1814-1826.
Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review
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