An Elite Archive-Assisted Multi-Objective Evolutionary Algorithm for mRNA Design

Wenjing Hong, Cheng Chen, Zexuan Zhu, Ke Tang

Abstract: Messenger RNA (mRNA) vaccines have emerged as highly effective strategies in the prophylaxis and treatment of diseases. mRNA design, a key to the success of mRNA vaccines, in-volves finding optimal codons and increasing secondary structure stability to lengthen mRNA half-life, ultimately enhancing protein expression. Despite receiving widespread attention, most methods primarily rely on manual design, which is time-consuming and labor-intensive. While optimization approaches can alleviate this issue, existing methods still exhibit critical limitations caused by conflicts between codon usage and mRNA structural stability, compounded by the vast design space of mRNA resulting from the presence of synonymous codons. In this paper, a novel multi-objective evolutionary optimization-based mRNA design method is proposed. We first formulate the mRNA design problem as a multi-objective optimization problem and then develop an Elite Archive-Assisted Multi-Objective Evolutionary algorithm for mRNA Design, namely EAA-MOED, by incorporating a novel elite archive-assisted method into a weighted optimization framework to improve search efficiency. Experimental studies, involving two state-of-the-art mRNA design methods and five well-known MOEAs, show the competitiveness of the proposed EAA-MOED in mRNA design.