mRNA Delivery Systems Recent Advances in Lipid Nanoparticles, Nanocarriers, Targeting Strategies, and Therapeutic Applications

Abstract

 

Messenger RNA (mRNA) has emerged as a promising therapeutic platform because it enables transient and programmable protein expression without permanent genomic modification. However, its clinical application is strongly dependent on efficient delivery systems capable of protecting mRNA from degradation, facilitating cellular uptake, promoting endosomal escape and enabling cytoplasmic release. This review examines recent advances in mRNA delivery systems between 2015 and 2025, with particular emphasis on lipid nanoparticles (LNPs), emerging nanocarriers and targeted delivery strategies. The literature demonstrates that ionisable lipid-based LNPs have become the most clinically advanced platform owing to their high encapsulation efficiency, favourable delivery performance and scalable manufacturing potential. Nevertheless, conventional LNPs remain associated with limitations including preferential hepatic accumulation, endosomal entrapment, inflammatory responses, stability concerns and challenges in achieving extrahepatic delivery. Advances in ionisable lipid chemistry, selective organ targeting, ligand-mediated targeting, polymeric nanoparticles, lipid–polymer hybrid systems, peptide-based carriers and extracellular vesicles are providing opportunities to address these limitations. The therapeutic scope of mRNA delivery has also expanded beyond vaccination towards cancer immunotherapy, protein replacement, gene editing, regenerative medicine and genetic disorders. Overall, current evidence indicates a transition from conventional mRNA formulations towards more precise, biodegradable, tissue-selective and application-specific nanocarriers. Continued integration of RNA engineering, nanomaterial chemistry, targeting biology and scalable manufacturing will be essential for improving safety, therapeutic efficacy and clinical translation of next-generation mRNA medicines.