Naturally Derived Membrane Lipids Impact Nanoparticle-Based Messenger RNA Delivery
Open accessAbstract
Introduction Lipid based nanoparticles (LNPs) are clinically successful vectors for hepatic delivery of nucleic acids. These systems are being developed for non-hepatic delivery of mRNA for the treatment of diseases like cystic fibrosis or retinal degeneration as well as infectious diseases. Localized delivery to the lungs requires aerosolization. We hypothesized that structural lipids within LNPs would provide features of integrity which can be tuned for attributes required for efficient hepatic and non-hepatic gene delivery. Herein, we explored whether naturally occurring lipids that originate from the cell membrane of plants and microorganisms enhance mRNA-based gene transfection in vitro and in vivo and whether they assist in maintaining mRNA activity after nebulization.Methods We substituted DSPC, a structural lipid used in a conventional LNP formulation, to a series of naturally occurring membrane lipids. We measured the effect of these membrane lipids on size, encapsulation efficiency and their impact on transfection efficiency. We further characterized LNPs after nebulization and measured whether they retained their transfection efficiency.Results One plant-derived structural lipid, DGTS, led to a significant improvement in liver transfection of mRNA. DGTS LNPs had similar transfection ability when administered in the nasal cavity to conventional LNPs. In contrast, we found that DGTS LNPs had reduced transfection efficiency in cells pre-and post-nebulization while maintaining size and encapsulation similar to DSPC LNPs.Conclusions We found that structural lipids provide differential mRNA-based activities in vitro and in vivo which also depend on the mode of administration. Understanding influence of structural lipids on nanoparticle morphology and structure can lead to engineering potent materials for mRNA-based gene therapy applications.
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Naturally derived membrane lipids can also be applied for mRNA delivery.
“Naturally derived membrane lipids (for example, exosomes and cell membranes) can also be applied for mRNA delivery116,249,250.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [116]
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- Authors
- Kim, J., Jozic, A., & Sahay, G.
- Affiliations
- Oregon State University (US)
- Corresponding author
- Sahay, Gaurav
- Venue
- Cellular and Molecular Bioengineering
- Published
- 2020-05-26
- Volume
- 13
- Issue
- 5
- Pages
- 463-474
- ISSN
- 1865-5025 (ISSN-L)
- 1865-5033
- PMC
- PMC7250267
- OpenAlex
- W3028921980
- Cited by
- 61
- References
- 51
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 18 · 2023: 6 · 2022: 12 · 2021: 11 · 2020: 2
- FWCI
- 2.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cellular and Molecular Bioengineering (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (1R01HL146736-01)
- National Institute of Biomedical Imaging and Bioengineering (1R15EB021581-01)
- Cystic Fibrosis Foundation Therapeutics (SAHAY18G0)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
- Keywords
- lipid nanoparticles, mRNA delivery, DSPC, intranasal drug delivery, nebulization, transfection efficiency, encapsulation efficiency, nanoparticle size
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