An overview of rational design of mRNA-based therapeutics and vaccines.

Extensive research efforts have been made to optimize mRNA constructs and preparation procedures to unleash the full potential of mRNA-based therapeutics and vaccines. Sequence optimization (untranslated region and codon usage), chemical engineering of nucleotides and modified 5'cap, and optimization of in vitro transcription and mRNA purification protocols have overcome the major obstacles (instability, delivery, immunogenicity and safety) hindering the clinical applications of mRNA therapeutics and vaccines. The optimized design parameters should not be applied as default to different biological systems, but rather individually optimized for each mRNA sequence and intended application. Further advancement in the mRNA design and delivery technologies for achieving cell type- and organ site-specificity will broaden the scope and usefulness of this new class of drugs.