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Viral Vectors for in Vivo Gene Transfer

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Abstract

The transfer of DNA into the nucleus of a eukaryotic cell (gene transfer) is a central theme of modern biology. The transfer is said to be somatic when it refers to non-germline organs of a developed individual, and germline when it concerns gametes or the fertilised egg of an animal, with the aim of transmitting the relevant genetic modification to its descendents [1]. The efficient introduction of genetic material into a somatic or germline cell and the control of its expression over time have led to major advances in understanding how genes work in vivo, i.e., in living organisms (functional genomics), but also to the development of innovative therapeutic methods (gene therapy). The efficiency of gene transfer is conditioned by the vehicle used, called the vector. Desirable features for a vector are as follows: Easy to produce high titer stocks of the vector in a reproducible way. Absence of toxicity related to transduction (transfer of genetic material into the target cell, and its expression there) and no immune reaction of the organism against the vector and/or therapeutic protein. Stability in the expression of the relevant gene over time, and the possibility of regulation, e.g., to control expression of the therapeutic protein on the physiological level, or to end expression at the end of treatment. Transduction of quiescent cells should be as efficient as transduction of dividing cells. Vectors currently used fall into two categories: non-viral and viral vectors. In non-viral vectors, the DNA is complexed with polymers, lipids, or cationic detergents (described in Chap. 3). These vectors have a low risk of toxicity and immune reaction. However, they are less efficient in vivo than viral vectors when it comes to the number of cells transduced and long-term transgene expression. (Naked DNA transfer or electroporation is rather inefficient in the organism. This type of gene transfer will not be discussed here, and the interested reader is referred to the review [2].) For this reason, it is mainly viral vectors that are used for gene transfer in animals and humans.

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Acknowledgements

The authors would like to thank Pascal Le Masson and Chamsy Sarkis, together with Aurélie Delzor, Mario Lepore, Jean-Charles Robillard, Anne-Sophie Chaplault, Sandro Alvès, Raymonde Hassig, and Carole Escartin for their invaluable contributions to this chapter.

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Authors and Affiliations

  1. Laboratoire des Processus Stochastiques et Spectres, Commissariat à l’Energie Atomique LIST, 91191, Gif-sur-Yvette, France

    E. Thévenot

  2. MIRCen CEA Fontenay-aux-Roses, 18 route du Panorama, 92265, Fontenay-aux-Roses Cedex, France

    N. Dufour & N. Déglon

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  1. E. Thévenot
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  2. N. Dufour
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  3. N. Déglon
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Correspondence to E. Thévenot .

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  1. LETI-MINATEC, CEA, rue des martyrs 17, Grenoble CX 9, 38054, France

    Patrick Boisseau

  2. Université d'Evry, bd. F. Mitterrand, Evry CX, 91025, France

    Philippe Houdy

  3. Dépt. Sciences des Matériaux, Université d'Evry, rue du père Jarlan, Evry CX, 91025, France

    Marcel Lahmani

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Thévenot, E., Dufour, N., Déglon, N. (2009). Viral Vectors for in Vivo Gene Transfer. In: Boisseau, P., Houdy, P., Lahmani, M. (eds) Nanoscience. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-88633-4_23

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