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Generation of Cationic Nanoliposomes for the Efficient Delivery of In Vitro Transcribed Messenger RNA
Published on: February 1, 2019
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Naturally Derived Membrane Lipids Impact Nanoparticle-Based Messenger RNA Delivery
Jeonghwan Kim1, Antony Jozic1, Gaurav Sahay1,2
1Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Robertson Life Sciences Building, Portland, OR USA.
Cellular and Molecular Bioengineering
|August 25, 2020
Summary
Naturally occurring lipids like DGTS can improve mRNA delivery in the liver but may reduce effectiveness after nebulization for lung delivery. Further research into structural lipids can optimize nanoparticle design for gene therapy.
Area of Science:
- Biotechnology
- Nanomedicine
- Molecular Biology
Background:
- Lipid-based nanoparticles (LNPs) are effective for delivering nucleic acids to the liver.
- Developing LNPs for non-hepatic mRNA delivery (e.g., cystic fibrosis, retinal degeneration, infectious diseases) requires aerosolization for lung delivery.
- Structural lipids influence LNP integrity and gene delivery efficiency.
Purpose of the Study:
- To investigate naturally occurring membrane lipids for enhanced mRNA gene transfection.
- To assess LNP performance for both hepatic and non-hepatic delivery, including post-nebulization.
- To explore the impact of structural lipids on mRNA activity and LNP integrity.
Main Methods:
- Substituted DSPC in conventional LNPs with naturally occurring membrane lipids.
- Evaluated effects on nanoparticle size, encapsulation efficiency, and transfection efficiency.
- Characterized LNPs post-nebulization to assess retained transfection efficiency.
Main Results:
- A plant-derived lipid, DGTS, significantly improved liver mRNA transfection.
- DGTS-LNPs showed comparable nasal cavity transfection to conventional LNPs.
- DGTS-LNPs exhibited reduced transfection efficiency post-nebulization, despite maintaining size and encapsulation.
Conclusions:
- Structural lipids differentially impact in vitro and in vivo mRNA delivery, influenced by administration route.
- Understanding structural lipid influence on LNP morphology is key for developing potent mRNA gene therapy materials.
