Engineered extracellular vesicles as next-generation platforms for mRNA therapeutics delivery

mRNA has emerged as a star molecule in pharmaceutical development, demonstrating immense potential for the diagnosis and treatment of cancer, neurological disorders, genetic diseases, and infectious diseases. It has played a particularly pivotal role in COVID-19 prevention. However, the clinical translation of mRNA therapeutics is significantly hampered by its inherent instability, low cellular permeability, and poor targeting specificity. Consequently, the development of efficient mRNA delivery systems represents a paramount challenge for its biomedical application. Conventional delivery platforms, as exemplified by lipid nanoparticles (LNPs), offer advantages including mature manufacturing processes and broad clinical adoption. Nevertheless, they still face limitations such as suboptimal delivery efficiency and biosafety concerns requiring further improvement. Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, have emerged as highly promising mRNA delivery vectors. This is attributed to their low immunogenicity, favorable biosafety profile, intrinsic homing effect-based targeting capability, and amenability to engineering modifications. This review comprehensively summarizes recent advances in EV-mediated mRNA delivery, detailing strategies for mRNA loading into EVs, approaches for achieving targeted mRNA delivery using EVs, and the therapeutic applications of EV-encapsulated mRNA. The synthesis of this knowledge aims to provide insights to advance the clinical implementation of mRNA-based therapeutics.