Biodistribution study of phosphonolipids: A class of non-viral vectors efficient in mice lung-directed gene transfer - Université de Bretagne Occidentale Access content directly
Journal Articles The Journal of Gene Medicine Year : 2003

Biodistribution study of phosphonolipids: A class of non-viral vectors efficient in mice lung-directed gene transfer

Abstract

Background: A multitude of cationic lipids have been synthesized since they were first proposed for use in gene therapy. Cationic lipids are able to efficiently transfect cells both in vitro and in vivo. Whereas most research groups have focused their investigations on the toxicity of these molecules, and on the location of expression of the DNA transferred by these vectors, little has been done to determine their biodistribution and elimination pathways. Our group has developed a family of cationic lipids termed phosphonolipids. Following a large in vitro screening experiment, we have selected several molecules for in vivo testing, with some of these phosphonolipids forming lipoplexes efficient in transfecting mouse lungs. It was thus of interest to study their fate after intravenous injection. Methods: The respective biodistributions of both the GLB43 phosphonolipid and plasmid DNA were investigated and compared with DNA expression sites. Using the optimal conditions determined for phosphonolipids, we followed the gene transfer agent and plasmid DNA distributions versus time by radiolabeling them with 14C and 32P, respectively. Otherwise, we performed imaging by radiolabeling plasmid DNA with 99mTc. Results: The lipoplexes appear to be directly located in the lung after administration. Secondly, the plasmid is released mainly into the lungs and the phosphonolipid vector is rapidly degraded. The hydrophilic moiety of the phosphonolipid is eliminated in the urine, as is the free plasmid. Conclusions: This study reveals that there are slight differences in the observed results depending on the technique used to label the DNA; secondly, results show that the residence time of phosphonolipids in the mouse body is related to the DNA binding time.
Fichier principal
Vignette du fichier
Delepine2003.pdf (183.61 Ko) Télécharger le fichier
Origin : Files produced by the author(s)

Dates and versions

hal-01763909 , version 1 (13-05-2022)

Licence

Attribution - NonCommercial

Identifiers

Cite

Pascal Delépine, Christine Guillaume, Tristan Montier, Jean-Claude Clément, Jean-Jacques Yaouanc, et al.. Biodistribution study of phosphonolipids: A class of non-viral vectors efficient in mice lung-directed gene transfer. The Journal of Gene Medicine, 2003, 5 (7), pp.600-608. ⟨10.1002/jgm.385⟩. ⟨hal-01763909⟩
70 View
66 Download

Altmetric

Share

Gmail Facebook X LinkedIn More