The Journal of Membrane Biology

, Volume 236, Issue 1, pp 61–74

Gene Transfer: How Can the Biological Barriers Be Overcome?

  • Jean-Michel Escoffre
  • Justin Teissié
  • Marie-Pierre Rols
Article

DOI: 10.1007/s00232-010-9275-0

Cite this article as:
Escoffre, JM., Teissié, J. & Rols, MP. J Membrane Biol (2010) 236: 61. doi:10.1007/s00232-010-9275-0

Abstract

Physical methods represent a promising approach for the safe delivery of therapeutic plasmid DNA in genetic and acquired human diseases. However, their development in clinics is limited by their low efficacy. At the cellular level, efficient gene transfer is dependent on several factors including extracellular matrix, plasmid DNA uptake and nucleocytoplasmic transport. We review the main barriers that plasmid DNA encounters from the extracellular environment toward the interior of the cell and the different strategies developed to overcome these biological barriers. Diffusional and metabolic fences of the extracellular matrix and the cytoplasm affect plasmid DNA uptake. These barriers reduce the number of intact plasmids that reach the nucleus. Nuclear uptake of plasmid DNA further requires either an increase of nuclear permeability or an active nuclear transport via the nuclear pore. A better understanding of the cellular and molecular bases of the physical gene-transfer process may provide strategies to overcome those obstacles that highly limit the efficiency and use of gene-delivery methods.

Keywords

Gene therapy Physical methods Extracellular matrix Plasma membrane Cytoplasm Nucleus 

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Jean-Michel Escoffre
    • 1
    • 2
  • Justin Teissié
    • 1
    • 2
  • Marie-Pierre Rols
    • 1
    • 2
  1. 1.CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale)ToulouseFrance
  2. 2.Université de Toulouse, UPS, IPBSToulouseFrance

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