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Gene Transfer: How Can the Biological Barriers Be Overcome?

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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.

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Acknowledgments

Many thanks are due to the financial support from the CNRS, the Association Française sur les Myopathies, the ANR “Cemirbio,” the ANR “CMIDT” and the Région Midi-Pyrénées. J.-M. E. was the recipient of a PhD fellowship of the French government

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  1. CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), 205 route de Narbonne, 31077, Toulouse, France

    Jean-Michel Escoffre, Justin Teissié & Marie-Pierre Rols

  2. Université de Toulouse, UPS, IPBS, 31077, Toulouse, France

    Jean-Michel Escoffre, Justin Teissié & Marie-Pierre Rols

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  1. Jean-Michel Escoffre
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  2. Justin Teissié
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Correspondence to Marie-Pierre Rols.

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Escoffre, JM., Teissié, J. & Rols, MP. Gene Transfer: How Can the Biological Barriers Be Overcome?. J Membrane Biol 236, 61–74 (2010). https://doi.org/10.1007/s00232-010-9275-0

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