Advances in high-throughput screening of cyclic peptide drugs using mRNA display technology.

mRNA display-derived cyclic peptides signals the approach's maturation. In this review, we systematically evaluate mRNA display technology by outlining its methodological framework and highlighting its unique advantages for engineering macrocyclic therapeutics. We critically examine its transformative potential as well as its inherent limitations in identifying bioactive cyclic peptides, with particular attention to library diversity and the precision of on-resin screening. Through this analysis, we aim to provide insightful perspectives and strategic recommendations to guide future efforts in exploiting mRNA display for the development of innovative cyclic peptide-based drugs.