mRNA序列优化

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研究提出mRNA序列优化平台提升药物研发效能
Jing Ji Guan Cha Wang· 2025-05-22 07:24
Core Insights - A new mRNA sequence design and optimization platform named mRNAdesigner has been developed by a collaborative team from various institutions, laying the groundwork for the next generation of nucleic acid drugs [1][2]. Group 1: mRNA Drug Development - mRNA drugs are becoming a significant focus in modern biomedicine, but current designs face challenges such as cross-species adaptability, neglect of upstream and downstream untranslated regions, and insufficient control of immunogenicity [2]. - The mRNAdesigner platform integrates cutting-edge research on RNA translation dynamics, optimizing mRNA sequence design by considering codon preference, GC content, and secondary structure impacts on protein translation [2]. Group 2: Optimization Features - The platform enables comprehensive optimization of key mRNA structural regions (5'UTR, CDS, 3'UTR), enhancing codon adaptation index and optimizing base pairing while avoiding long stem-loop structures and GC-rich areas, thus reducing the risk of natural immune recognition and degradation [2]. - For the 5'UTR region, the platform improves ribosome loading (MRL) to enhance translation initiation and elongation efficiency [2]. - In the 3'UTR region, the platform employs regulatory element annotation algorithms to identify and reduce the number of degradation-related regulatory elements, thereby improving overall mRNA stability [2]. Group 3: Experimental Validation - Simulations and experimental evaluations indicate that mRNA sequences generated by mRNAdesigner show improvements in codon adaptability, base pairing rates, and reduction of long stem-loop structures compared to wild-type sequences, resulting in higher protein expression levels in eukaryotic cell systems [3]. - The research findings have been published in the journal Nucleic Acids Research, providing robust support for nucleic acid vaccine development, protein drug production, and molecular biology research [3].