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Updated: Aug 14, 2026
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Generation of Cationic Nanoliposomes for the Efficient Delivery of In Vitro Transcribed Messenger RNA
Published on: February 1, 2019
Hyperbranched Polylysine-Based Lipopolyplexes Enable Efficient mRNA Delivery With Long-Term Storage Stability
Huidi Meng1,2, Bingjie Fu1,2, Min Liang2
1College of Engineers, Zhejiang University, Hangzhou, China.
Advanced Healthcare Materials
|August 13, 2026
Summary
A novel hyperbranched poly-L-lysine (HBPL) core enhances messenger RNA (mRNA) delivery systems, improving storage stability and cellular uptake for advanced mRNA therapeutics and vaccines.
Area of Science:
- Biotechnology
- Polymer Chemistry
- Nanomedicine
Background:
- Clinical translation of mRNA therapeutics is limited by the poor storage stability of lipid-based delivery vectors.
- Conventional lipopolyplex (LPP) systems often fail to achieve efficient nucleic acid release via membrane fusion.
Purpose of the Study:
- To develop a novel ternary LPP platform using hyperbranched poly-L-lysine (HBPL) for improved mRNA delivery.
- To overcome limitations in mRNA therapeutic delivery, focusing on stability, release efficiency, and biocompatibility.
Main Methods:
- Incorporation of HBPL as a functional core in lipid/HBPL/mRNA LPPs.
- Evaluation of mRNA encapsulation efficiency, colloidal stability, and cellular uptake mechanisms (membrane fusion).
- Assessment of in vitro transfection efficiency, dendritic cell maturation, and in vivo delivery to lungs and spleen.
Main Results:
- The HBPL-based LPP platform demonstrated high mRNA encapsulation, efficient intracellular release, and exceptional colloidal stability.
- The platform promoted cellular uptake via membrane fusion, leading to efficient cytoplasmic delivery and superior mRNA release compared to linear PLL counterparts.
- High transfection efficiency, enhanced dendritic cell maturation, and superior biocompatibility were observed, with sustained protein expression in vivo for over 1 month.
Conclusions:
- The HBPL-based LPP platform successfully integrates long-term stability with high delivery efficiency for mRNA therapeutics.
- This novel platform overcomes key limitations of conventional lipid nanoparticles, showing significant promise for advancing mRNA therapeutics and vaccines.
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