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An improved self-deleting retroviral vector derived from avian leukemia and sarcoma virus

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Abstract

We have previously developed a self-deleting avian leukosis and sarcoma virus (ALSV)- based retroviral vector carrying an additional attachment (att) sequence. Resulting proviruses underwent deletion of viral sequences and were flanked either by two LTRs (LTRs proviruses) or by the additional att sequence and the 3′ LTR (att proviruses). Herein, we have tried to increase (1) the self-deleting properties of this vector, either by raising the selection pressure applied on target cells or by optimizing the size of the internal att sequence, (2) the titer of the vector by deleting or inverting some viral sequences. Moreover, a new type of provirus flanked by att sequences at each end was isolated. Finally, under specific conditions, 100% of proviruses had internal sequences deleted, and as many as 92–100% of proviruses were no longer mobilizable by a replication-competent virus. The inactivation procedure achieved here might improve the biosafety of retroviral vectors.

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Acknowledgments

This work was supported by research grants from the Institut National de la Recherche Agronomique (INRA), the Centre National de la Recherche Scientifique (CNRS), and the Association pour la Recherche sur le Cancer (ARC). We thank Transgene SA (Strasbourg), the INRA and the Ligue Nationale Contre le Cancer for fellowships (CTC) and the Ministère de l’Education Nationale et de la Recherche (MENRT) for fellowships (KM). Special thanks to Dr. Antoine Drynda and Dr. Yahia Chebloune for their helpful contributions to this work as well as to Dr. Christophe Terzian for statistical analyses. Thanks are also due to Dr. M. Mehtali (Transgene) and collaborators for fruitful discussions and to the INRA translation service for correction of the English.

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Authors and Affiliations

  1. Université de Lyon, Lyon, France

    Caroline Torne-Celer, Karen Moreau, Claudine Faure, Gérard Verdier & Corinne Ronfort

  2. INRA, UMR754 Rétrovirus et Pathologie Comparée, IFR128 Biosciences Gerland-Lyon Sud, Lyon, France

    Karen Moreau, Gérard Verdier & Corinne Ronfort

  3. Université Lyon 1, 69007, Lyon, France

    Caroline Torne-Celer, Karen Moreau, Claudine Faure, Gérard Verdier & Corinne Ronfort

  4. Ecole Nationale Vétérinaire de Lyon, 69000, Marcy L’étoile, France

    Karen Moreau, Gérard Verdier & Corinne Ronfort

  5. Ecole Pratique des Hautes Etudes, Lyon, France

    Karen Moreau, Gérard Verdier & Corinne Ronfort

  6. CNRS, Centre de Génétique Moléculaire et Cellulaire, 69622, Villeurbanne, France

    Caroline Torne-Celer & Claudine Faure

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  1. Caroline Torne-Celer
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  2. Karen Moreau
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  3. Claudine Faure
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  4. Gérard Verdier
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  5. Corinne Ronfort
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Correspondence to Corinne Ronfort.

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Torne-Celer, C., Moreau, K., Faure, C. et al. An improved self-deleting retroviral vector derived from avian leukemia and sarcoma virus. Arch Virol 153, 2233–2243 (2008). https://doi.org/10.1007/s00705-008-0252-1

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  • DOI: https://doi.org/10.1007/s00705-008-0252-1

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