Incorporation of phosphatidylserine improves efficiency of lipid based gene delivery systems.

Gene Transfer Techniques Liposomes Nanoparticles Phosphatidylserines RNA, Messenger / genetics
Lipid composition Lipid nanoparticles Nucleic acid delivery Phosphatidylserine Transfection efficiency Transfection potency

Journal

European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
ISSN: 1873-3441
Titre abrégé: Eur J Pharm Biopharm
Pays: Netherlands
ID NLM: 9109778

Informations de publication

Date de publication:
Mar 2022
Historique:
received: 05 11 2021
revised: 11 02 2022
accepted: 11 02 2022
pubmed: 20 2 2022
medline: 5 4 2022
entrez: 19 2 2022
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.ejpb.2022.02.007 PMID: 35181492
pubmed: 35181492
pii: S0939-6411(22)00028-5
doi: 10.1016/j.ejpb.2022.02.007
pii:
doi:

Substances chimiques

Lipid Nanoparticles 0
Liposomes 0
Phosphatidylserines 0
RNA, Messenger 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

134-143

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.

Auteurs

Claudia Lotter (C)

Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland.

Claudio Luca Alter (CL)

Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland; Swiss Nanoscience Institute, University of Basel, Klingelbergstrasse 82, 4056 Basel, Switzerland.

Jan Stephan Bolten (JS)

Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland.

Pascal Detampel (P)

Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland.

Cornelia G Palivan (CG)

Swiss Nanoscience Institute, University of Basel, Klingelbergstrasse 82, 4056 Basel, Switzerland; Department of Chemistry, University of Basel, Mattenstrasse 24a, BPR 1096, 4003 Basel, Switzerland.

Tomaž Einfalt (T)

Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland.

Jörg Huwyler (J)

Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland. Electronic address: joerg.huwyler@unibas.ch.

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Classifications MeSH

questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Techniques de transfert de gènes › Incorporation of phosphatidylserine improves...
questionsmedicales.fr › Technologie, industrie et agriculture › Produits manufacturés › Matériaux biomimétiques › Membrane artificielle › Liposomes › Incorporation of phosphatidylserine improves...
questionsmedicales.fr › Technologie, industrie et agriculture › Produits manufacturés › Nanostructures › Nanoparticules › Incorporation of phosphatidylserine improves...
questionsmedicales.fr › Lipides › Lipides membranaires › Phospholipides › Glycérophosphate › Acides phosphatidiques › Glycérophospholipides › Phosphatidylsérine › Incorporation of phosphatidylserine improves...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN messager › Incorporation of phosphatidylserine improves...