A novel deep generative model for mRNA vaccine development : Designing 5′ UTRs with N1-methyl-pseudouridine modification

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

3 Scopus Citations
View graph of relations

Author(s)

  • Xiaoshan Tang
  • Yuting Chen
  • Hai Huang
  • Shugang Qin
  • Zeyi Qin
  • Xin Jiang
  • Yongmei Liu
  • Xing Duan
  • Hao Li
  • Na Fan
  • Zhongshan He
  • Xi He
  • Bairong Shen
  • Xiangrong Song

Related Research Unit(s)

Detail(s)

Original languageEnglish
Pages (from-to)1814-1826
Number of pages13
Journal / PublicationActa Pharmaceutica Sinica B
Volume14
Issue number4
Online published5 Nov 2023
Publication statusPublished - Apr 2024

Link(s)

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.

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

Download Statistics

No data available