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  • Viral Transfer Technology
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Transcriptionally active drugs improve adenovirus vector performance in vitro and in vivo

Gene Therapy volume 7, pages 1624–1630 (2000)Cite this article

Abstract

Cytomegalovirus (CMV) promoter is often present in recombinant adenovirus vectors (AdVs) suitable for gene therapy, ensuring high levels of transgene production in a wide range of hosts. Despite this characteristic, the presence of the AdV genome in target cells and tissues typically lasts longer than transgene production that may be rapidly extincted by ill-defined silencing mechanisms. In the present article, it is reported that transcriptionally active drugs, retinoic acid (RA) and histone deacetylase inhibitor trichostatin A (TSA), enhance AdV transgene expression in infected cells and tissues. The association of RA and TSA increased more than seven-fold above control the activity of AdVs encoding for LacZ or VEGF165. This effect was, at least in part, mediated by the direct activation of retinoic acid receptors. Finally, administration of RA and TSA alone at days 0 and 5 after infection prolonged transgene production up to 21 days after infection versus 6–8 days in untreated controls. These results indicate that transcriptionally active drugs improve AdV function and may represent a novel strategy to more efficiently design AdVs for gene therapy interventions.

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Acknowledgements

This work has been partially supported by grants from the European Union (Biomed96 1160, Biomed97 2270), Telethon (A61) and AIRC. The authors would like to thank Professor Frank Graham for encouragement and helpful discussion of results during the progress of this work. Special thanks to Mrs Gabriella Ricci and Miss Cinzia Carloni for help in typing and editing of this manuscript.

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Author notes

  1. C Gaetano and A Catalano: The first two authors contributed equally to this work

Authors and Affiliations

  1. Laboratorio di Patologia Vascolare, Istituto Dermopatico dell'Immacolata, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy

    C Gaetano, A Catalano, R Palumbo, B Illi, G Ventoruzzo, F Serino & M C Capogrossi

  2. Dipartimento di Oncologia e Neuroscienze, Sezione di Patologia Clinica, Facoltà di Medicina e Chirurgia, Università ‘G D'Annunzio’, Chieti, Italy

    A Catalano

  3. Cattedra di Semeiotica Chirugica, Università Cattolica del Sacro Cuore, Via della Pineta Sacchetti, Rome, Italy

    G Orlando

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  1. C Gaetano
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Gaetano, C., Catalano, A., Palumbo, R. et al. Transcriptionally active drugs improve adenovirus vector performance in vitro and in vivo. Gene Ther 7, 1624–1630 (2000). https://doi.org/10.1038/sj.gt.3301296

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