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Using Lipid Nanoparticles for the Delivery of Chemically Modified mRNA into Mammalian Cells
Published on: June 10, 2022
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Efficient mRNA delivery using lipid nanoparticles modified with fusogenic coiled-coil peptides
Ye Zeng1, Mengjie Shen1, Roy Pattipeiluhu1
1Department of Supramolecular & Biomaterials Chemistry, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands. a.kros@chem.leidenuniv.nl.
Nanoscale
|September 6, 2023
Summary
Researchers developed a novel gene delivery system using fusogenic coiled-coil peptides to improve lipid nanoparticle (LNP) efficiency. This method enhances cellular uptake and protein expression, overcoming endosomal entrapment for effective gene therapy.
Area of Science:
- Biotechnology
- Molecular Biology
- Gene Therapy
Background:
- Gene delivery is crucial for treating diseases by modulating protein expression.
- Current nonviral gene delivery systems, like lipid nanoparticles (LNPs), face challenges with cellular internalization and endosomal escape.
- Inefficient endosomal escape limits the therapeutic potential of many gene delivery strategies.
Purpose of the Study:
- To develop a highly efficient gene delivery system using fusogenic coiled-coil peptides.
- To enhance the cellular uptake and cytosolic delivery of nucleic acids encapsulated in LNPs.
- To overcome the limitations of endosomal entrapment in gene therapy applications.
Main Methods:
- Modification of lipid nanoparticles (LNPs) carrying EGFP-mRNA with complementary coiled-coil lipopeptides.
- Modification of target cells with complementary coiled-coil lipopeptides.
- Utilizing coiled-coil peptide interactions to promote nucleic acid delivery.
Main Results:
- Coiled-coil formation between modified LNPs and cells led to rapid nucleic acid uptake.
- Enhanced expression of Green Fluorescent Protein (GFP) was observed, indicating successful gene delivery.
- Cellular uptake mechanism appeared to involve membrane fusion, bypassing traditional endocytosis pathways.
Conclusions:
- Fusogenic coiled-coil peptide modification significantly enhances LNP-mediated gene delivery efficiency.
- Direct cytosolic delivery via membrane fusion circumvents endosomal escape issues.
- This strategy holds promise for improving various gene therapy applications.
