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Incorporation of phosphatidylserine improves efficiency of lipid based gene delivery systems

Lotter, Claudia and Alter, Claudio Luca and Bolten, Jan Stephan and Detampel, Pascal and Palivan, Cornelia G. and Einfalt, Tomaž and Huwyler, Jörg. (2022) Incorporation of phosphatidylserine improves efficiency of lipid based gene delivery systems. European Journal of Pharmaceutics and Biopharmaceutics, 172. pp. 134-143.

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Abstract

The essential homeostatic process of dead cell clearance (efferocytosis) is used by viruses in an act of apoptotic mimicry. Among others, virions leverage phosphatidylserine (PS) as an essential "eat me" signal in viral envelopes to increase their infectivity. In a virus-inspired biomimetic approach, we demonstrate that PS can be incorporated into non-viral lipid nanoparticle (LNP) pDNA/mRNA constructs to enhance cellular transfection. The inclusion of the bioactive PS leads to an increased ability of LNPs to deliver nucleic acids in vitro to cultured HuH-7 hepatocellular carcinoma cells resulting in a 6-fold enhanced expression of a transgene. Optimal PS concentrations are in the range of 2.5 to 5% of total lipids. PS-decorated mRNA-LNPs show a 5.2-fold enhancement of in vivo transfection efficiency as compared to mRNA-LNPs devoid of PS. Effects were less pronounced for PS-decorated pDNA-LNPs (3.2-fold increase). Incorporation of small, defined amounts of PS into gene delivery vectors opens new avenues for efficient gene therapy and can be easily extended to other therapeutic systems.
Faculties and Departments:05 Faculty of Science > Departement Chemie > Chemie > Physikalische Chemie (Palivan)
05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Pharmaceutical Technology (Huwyler)
UniBasel Contributors:Huwyler, Jörg and Lotter, Claudia and Alter, Claudio and Bolten, Jan Stephan and Detampel, Pascal and Palivan, Cornelia G and Einfalt, Tomaž
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Elsevier
ISSN:0939-6411
e-ISSN:1873-3441
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:16 May 2022 07:22
Deposited On:16 May 2022 07:22

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