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Efficient gene transfer and long-term expression in neurons using a recombinant adenovirus with a neuron-specific promoter

Gene Therapy volume 6, pages 1884–1892 (1999)Cite this article

Abstract

Adenoviruses are highly efficient vectors for gene transfer into brain cells. Restricting transgene expression to specific cell types and maintaining long-term expression are major goals for gene therapy in the central nervous system. We targeted gene expression to neurons by constructing an adenoviral vector that expressed the E. coli LacZ reporter gene under the control of the rat neuron-specific enolase promoter (Ad-NSE). Expression from Ad-NSE was compared with that from an adenoviral vector encoding the same reporter gene under the control of the Rous sarcoma virus LTR promoter (Ad-RSV). Both recombinant adenoviruses were injected stereotactically into rat hippocampus, cerebellum and striatum. Anatomical and immunohistochemical analyses of the Ad-NSE-stained cells showed that neurons were preferentially transduced. More neurons were stained in the hippocampus following infection with Ad-NSE than with Ad-RSV. Cytotoxicity from Ad-NSE was lower than from Ad-RSV. β-Galactosidase gene expression after Ad-NSE infection remained stable for 3½ months, and was detectable for 6 months. Thus, the NSE-adenoviral vector can be used to transfer potentially therapeutic genes into neuronal cells. The use of a cell-specific promoter also resulted in high in vivo efficiency and long-term transgene expression.

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Acknowledgements

The authors thank M Barkats for critical reading of the manuscript, M Le Bert for generously providing pNSE, the NSE promoter fragment of which was obtained from G Sutcliffe. We also thank V Ridoux for assistance. This work was supported by grants from the Centre National de la Recherche Scientifique, Rhône-Poulenc Rorer, the Association Française contre les Myopathies, the Association Française Retinis Pigmentosa, and the Institut de Recherche sur la Moelle Epinière. VN was supported by the Assistance Publique-Hôpitaux de Paris, SM by the Ministère de l’Education Nationale de l’Enseignement Supérieur et de la Recherche.

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  1. G Le Gal La Salle

    Present address: Laboratoire d’Epileptologie Expérimentale et Clinique, Université Victor Ségalem, Bordeaux, France

Authors and Affiliations

  1. Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs, Bâtiment CERVI, Hôpital de la Pitié-Salpêtrière, Paris, France

    V Navarro, S Millecamps, M-C Geoffroy, J-J Robert & J Mallet

  2. Institut Alfred Fessard, CNRS, Gif sur Yvette, France

    A Valin & G Le Gal La Salle

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  1. V Navarro
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Navarro, V., Millecamps, S., Geoffroy, MC. et al. Efficient gene transfer and long-term expression in neurons using a recombinant adenovirus with a neuron-specific promoter. Gene Ther 6, 1884–1892 (1999). https://doi.org/10.1038/sj.gt.3301008

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