Fundamental Research · 3 authors, 3 centres
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This narrative review describes the evolution of mRNA therapeutics from proof-of-concept to commercialized COVID-19 vaccines and surveys emerging platforms including circular RNA and self-amplifying RNA alongside delivery technologies such as LNPs, polymers, and peptides. The authors identify ongoing challenges—immune stimulation, expression durability, and targeted delivery—and outline potential solutions for expanding mRNA applications beyond prophylactic vaccines.
They review preclinical and mechanistic studies of polymer-based (PEI, poly(β-amino esters), polyamides), pH-responsive, and peptide-based delivery systems, largely evaluated in mouse models. Key challenges remain in achieving minimal immunogenicity, long-term expression, and efficient tissue-specific delivery. The review highlights the role of the COVID-19 pandemic in accelerating mRNA technology maturation and suggests that advances in delivery and RNA engineering will broaden applications to protein replacement, cancer immunotherapy, and in vivo cell programming.
