mRNA-Based Therapeutics: Advances in Drug Delivery, Comparative Innovations, and Biomedical Applications.

mRNA-based therapeutics represent a major advancement in modern medicine, offering programmable and nonintegrating treatment options for infectious diseases, malignancies, and hereditary disorders. This review addresses the chronological evolution, structural optimization, and delivery challenges of mRNA drugs, highlighting developments such as nucleoside modifications and lipid nanoparticle (LNP) platforms that improve the stability and promote cellular entry. Comparative analysis highlights the benefits of mRNA over DNA-, siRNA-, and protein-based medicine in safety, scalability, and rapid rearrangement. Applications vary from COVID-19 vaccines to individualized cancer immunotherapy and protein replacement strategies. New methods, including self-amplifying mRNA (saRNA), CRISPR-Cas9 gene editing, and tissue-specific delivery systems, enhance the therapeutic potential. While mRNA technology faces challenges in terms of immunogenicity, multiple dosing, and durability of safety considerations, it offers unparalleled precision, transient expression, and swift manufacturability. This review emphasizes the comparative design principles of mRNA delivery systems, bridging formulation innovation with translational biomedical applications. By integrating lipid-based and nonlipid nanocarrier insights, it highlights critical advances shaping next-generation mRNA therapeutics.