Personalized Two-Stage mRNA-Encoded Blocker Strategy for Asthma

This research concept paper presents a proposed personalized two-stage mRNA-encoded therapeutic blocker strategy for asthma, focusing on IL-4Rα-associated inflammatory signaling. Stage 1 investigates the hypothesis of inducing antigen-specific immune nonresponsiveness to a defined therapeutic blocker protein. Stage 2 considers transient mRNA-mediated expression of an analytically matched blocker. The paper integrates clinical and preclinical evidence, the Rami Five-Checkpoint Framework, public human IL4RA FASTA reference sequences, and mathematical models involving codon adaptation, RNA structure, immunogenicity screening, and protein-expression dynamics.