mRNAdesigner: an integrated web server for optimizing mRNA design and protein translation in eukaryotes

Area of Science:

• Biotechnology
• Molecular Biology
• Bioinformatics

Background:

• Messenger RNA (mRNA) therapy has emerged as a revolutionary medical approach due to its rapid development and efficacy in inducing immune responses, particularly against infectious diseases.
• The efficiency of mRNA therapeutics is significantly influenced by the translational efficiency and stability of the mRNA sequence.
• Optimization of mRNA sequences involves modifications to 5' and 3' untranslated regions (UTRs), codon adaptation index, GC content, and secondary structures.

Purpose of the Study:

• To develop a web server, mRNAdesigner, for optimizing mRNA design to enhance stability and translational efficiency in eukaryotic systems.
• To provide researchers with a tool for designing high-expression mRNA sequences for protein production.

Main Methods:

• mRNAdesigner accepts coding sequences (CDS) and optional 5' and 3' UTRs as input.
• The tool optimizes CDS by minimizing unpaired regions and complex stem-loop structures, and mitigating rare codon usage.
• It also identifies optimal UTR sequences to improve translation efficiency and stability, while adhering to user-defined GC content.

Main Results:

• mRNAdesigner enables the optimization of full-length mRNA sequences for improved protein expression.
• The tool facilitates the generation of high-expression mRNA sequences suitable for eukaryotic expression systems.
• This computational resource is publicly accessible, supporting vaccine development and protein therapeutics.

Conclusions:

• mRNAdesigner is the first open-access tool designed to optimize mRNA sequences for enhanced stability and translational efficiency.
• This resource empowers researchers to design superior mRNA constructs for efficient protein production.
• The tool significantly aids in the advancement of mRNA-based vaccines and therapeutic applications.