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Testing the In Vitro and In Vivo Efficiency of mRNA-Lipid Nanoparticles Formulated by Microfluidic Mixing
Published on: January 20, 2023
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A Combinatorial Library of Lipid Nanoparticles for Cell Type-Specific mRNA Delivery
Gonna Somu Naidu1,2,3,4, Seok-Beom Yong1,2,3,4,5, Srinivas Ramishetti1,2,3,4
1Laboratory of Precision Nanomedicine, The Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel-Aviv, 69978, Israel.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|April 24, 2023
Summary
Researchers developed novel ionizable lipid nanoparticles (LNPs) for targeted mRNA delivery. Lipid 16 specifically targets CD11b macrophages, while Lipid 23 shows liver-specific delivery, advancing RNA therapeutics.
Area of Science:
- Biotechnology
- Nanomedicine
- Drug Delivery
Background:
- Ionizable lipid-based nanoparticles (LNPs) are advanced non-viral systems for RNA therapeutics and vaccines.
- Achieving cell type-specific, extrahepatic mRNA delivery remains a significant challenge for novel therapeutic development.
Purpose of the Study:
- To synthesize and evaluate a novel library of ionizable lipids for improved mRNA delivery.
- To identify specific ionizable lipids for potent, cell-type specific mRNA delivery beyond the liver.
Main Methods:
- Synthesis of a novel ionizable lipid library with modified hydrophobic tails and linkers.
- Formation of stable LNPs using microfluidic mixing with helper lipids.
- In vitro and in vivo evaluation of LNP-mediated mRNA delivery using reporter genes and an animal model.
Main Results:
- Branched ester tail chains with hydroxylamine linkers were found to reduce mRNA delivery efficiency in vitro.
- Lipid 23 demonstrated liver-specific mRNA delivery in vivo.
- Lipid 16 enabled potent, cell-type specific mRNA delivery to CD11b macrophages without targeting moieties.
- Compared to SM-102 based LNPs, novel LNPs showed improved cell-specific delivery and comparable toxicity.
Conclusions:
- The structural combination of lipid tails and linkers significantly influences LNP functionality and targeting.
- Novel ionizable lipids offer potential for targeted extrahepatic mRNA delivery, expanding therapeutic applications.
- Lipid 16 and Lipid 23 represent promising candidates for specific macrophage and liver mRNA delivery, respectively.
