Deep generative optimization of mRNA codon sequences for enhanced mRNA translation and therapeutic efficacy.

ABSTRACT: Messenger RNA (mRNA) therapeutics show immense promise, but their efficacy is limited by suboptimal protein expression. Here, we present RiboDecode, a deep learning framework that generates mRNA codon sequences for enhanced mRNA translation. RiboDecode introduces several advances, including direct learning from large-scale ribosome profiling data and generative exploration of a large sequence space. In silico analysis demonstrates RiboDecode's robust predictive accuracy for unseen genes and cellular environments. In vitro experiments showed substantial improvements in protein expression, significantly outperforming past methods. In addition, RiboDecode enables mRNA design with consideration of cellular context and demonstrates robust performance across different mRNA formats, including m

SUBMITTER: Li Y 

PROVIDER: S-EPMC12612108 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature