Polymer-Based Gene Delivery: A Current Review on the Uptake and Intracellular Trafficking of Polyplexes - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Current Gene Therapy Année : 2008

Polymer-Based Gene Delivery: A Current Review on the Uptake and Intracellular Trafficking of Polyplexes

Gilles Breuzard
Jean-Pierre Gomez
  • Fonction : Auteur
  • PersonId : 879249
Chantal Pichon

Résumé

Lipoplexes and polyplexes, electrostatic complexes between a plasmid DNA and cationic lipids or polymers are chemical systems that are developed for gene delivery. Considerable efforts have been done to delineate the exact knowledge of their entry mechanisms and the intracellular routing of the plasmid DNA that are of major importance for the designing of these gene delivery systems. While the uptake of lipoplexes made with several types of cationic lipids proceeds mainly by the clathrin-dependent pathway, it appears that for polyplexes the uptake pathway is more dependent on the polymer and the cell types. So, after an overview of the current knowledge of different endocytic pathways, we present here a selection of current reports related to the entry mechanisms and intracellular routing of plasmid DNA complexed with select cationic polymers. The review includes the role of glycosaminoglycans, cell polarization and cell cycle in the polyplex uptake and their transfection efficiency. We also report current data showing that the insertion of specific B motifs in the nucleic acid sequence provides an increase of the plasmid import into the nucleus. This has been demonstrated by fluorescence methods suitable to investigate the intracellular trafficking of pDNA. Overall, it appears that polyplex uptake proceeds both by the clathrin-dependent pathway and a clathrin-independent (cholesterol-dependent) pathway. These two entry mechanisms are not exclusive and can occur simultaneously in the same cell. Both of them lead to cell transfection but polyplexes still need improvements for clinical use.
Fichier non déposé

Dates et versions

hal-00518197 , version 1 (16-09-2010)

Identifiants

  • HAL Id : hal-00518197 , version 1

Citer

Patrick Midoux, Gilles Breuzard, Jean-Pierre Gomez, Chantal Pichon. Polymer-Based Gene Delivery: A Current Review on the Uptake and Intracellular Trafficking of Polyplexes. Current Gene Therapy, 2008, 8 (5), pp.335-352. ⟨hal-00518197⟩
129 Consultations
0 Téléchargements

Partager

Gmail Facebook X LinkedIn More