Advances in the Development of Lipid Nanoparticles for mRNA Delivery

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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Publication Details

Journal
Small Structures
Published
2026-02-01
DOI
https://doi.org/10.1002/sstr.202500568
Primary Topic
RNA Interference and Gene Delivery
Type
article
Field-Weighted Citation Impact
0.00
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article

Advances in the Development of Lipid Nanoparticles for mRNA Delivery

Letao Xu, Yue Hui, Chunxia Zhao, Yun Liu et al.
Small Structures
RNA Interference and Gene Delivery
article

Advances in the Development of Lipid Nanoparticles for mRNA Delivery

Letao Xu, Yue Hui, Chunxia Zhao, Yun Liu, Zhenwei Lan, Xing Wang
article en

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.

Small StructuresVol. 7(2)
The University of Adelaide (AU)
Openalex Percentile: Top 64%
RNA Interference and Gene Delivery
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Advances in the Development of Lipid Nanoparticles for mRNA Delivery — Letao Xu, Yue Hui, et al. · Small Structures (2026) | TGRS Research Map | TGRS