Advances in the Development of Lipid Nanoparticles for mRNA Delivery
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Date
2026
Authors
Wang, X.
Xu, L.
Lan, Z.
Hui, Y.
Liu, Y.
Yang, G.
Zhao, C.X.
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Journal article
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Small Structures, 2026; 7(2):e202500568-1-e202500568-37
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Xing Wang, Letao Xu, Zhenwei Lan, Yue Hui, Yun Liu, Guangze Yang, Chun-Xia Zhao
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Abstract
mRNA-based therapies have emerged as a versatile and transformative modality, highlighted by the global success of mRNA vaccines. Despite this progress, the broader clinical translation of mRNA therapeutics remains challenging due to their intrinsic instability, inefficient endosomal escape, and limited delivery efficiency, particularly to extrahepatic tissues. Lipid nanoparticles (LNPs) have proven central to overcoming these challenges, providing effective vehicles for mRNA protection and cellular delivery. In this review, we summarise the fundamental composition of LNPs and their roles in enabling mRNA therapeutics. We discuss scalable manufacturing strategies that support large-scale production, as well as advanced characterisation methods that elucidate critical structure–activity relationships. We also examine how tuning the physicochemical properties of LNPs can enhance transfection efficiency, improve target specificity, and determine in vivo behaviour. Furthermore, we highlight high-throughput screening approaches, including DNA barcoding, that accelerate the discovery of optimised formulations. Finally, we examine key safety considerations and emphasise that future progress in mRNA–LNP development will require multidisciplinary collaboration to balance efficacy with safety.
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© 2026 The Author(s). Small Structures published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited