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Recent Advances in mRNA-LNP Delivery Systems for Extrahepatic Organs: A Review
Ying Bai1,2,3, Li Cui1,2,3, Tianshu Liu1,2,3
1Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Molecular Pharmaceutics
|July 11, 2025
Summary
Lipid nanoparticles (LNPs) enhance mRNA therapy but face challenges in liver targeting and endosomal escape for extrahepatic diseases. This review explores solutions for next-generation intelligent LNPs.
Area of Science:
- Biotechnology
- Nanomedicine
- Gene Therapy
Background:
- Lipid nanoparticles (LNPs) are crucial for mRNA therapy, utilizing pH-dependent lipids for endosomal escape and cytoplasmic translation.
- Current LNP technology suffers from high non-specific liver accumulation (30-90%) and low endosomal escape efficiency (1-4%), limiting extrahepatic applications.
Purpose of the Study:
- To systematically review LNP molecular composition and structure-function relationships.
- To identify obstacles in extrahepatic LNP delivery.
- To propose strategies for enhancing organ selectivity and endosomal escape.
Main Methods:
- Literature review of LNP technology in mRNA therapy.
- Analysis of LNP molecular composition and structure-property correlations.
- Exploration of preclinical data on LNP delivery challenges and solutions.
Main Results:
- Identified significant challenges in LNP organ targeting and endosomal escape for extrahepatic delivery.
- Discussed molecular factors influencing LNP behavior and delivery efficiency.
- Highlighted preclinical findings on strategies to improve LNP performance.
Conclusions:
- Next-generation LNPs require enhanced organ selectivity and endosomal escape mechanisms.
- Addressing immune responses and large-scale production quality control are critical for clinical translation.
- A multidisciplinary approach is needed to develop intelligent LNPs for broader therapeutic applications.
