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Genomic DNA transfer with a high-capacity adenovirus vector results in improved in vivo gene expression and decreased toxicity

Nature Genetics volume 18, pages 180–183 (1998)Cite this article

A Correction to this article was published on 01 March 1998

Abstract

Many applications for human gene therapy would be facilitated by high levels and long duration of physiologic gene expression. Adenoviral vectors are frequently used for gene transfer because of their high cellular transduction efficiency in vitro and in vivo. Expression of viral proteins and the low capacity for foreign DNA limits the clinical application of first- and second-generation ade-noviral vectors1–7. Adenoviral vectors with all viral coding sequences deleted8–15 offer the prospect of decreased host immune responses to viral proteins, decreased cellular toxicity of viral proteins and increased capacity to accommodate large regulatory DNA regions. Currently most vectors used in vivo for preclinical and clinical studies express cDNAs under the control of heterologous eukaryotic or viral promoters. Using an adenoviral vector with all viral coding sequences deleted and containing the complete human α1-antitrypsin (PI) locus, we observed tissue-specific transcriptional regulation in cell culture and in vivo; intravenous injection in mice resulted in high levels of very stable expression for more than ten months and decreased acute and chronic toxicity. These results indicate significant advantages of regulated gene expression using genomic DNA for gene transfer and of adenoviral gene transfer vectors devoid of all viral coding sequences.

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Author notes

  1. Gudrun Schiedner & Stefan Kochanek

    Present address: Center for Molecular Medicine, University of Cologne, Kerpenerstraβe 34, 50931, Cologne, Germany

Authors and Affiliations

  1. Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, 77030, USA

    Gudrun Schiedner, Núria Morral, Ying Wu, Suzanne C. Koopmans, Arthur L. Beaudet & Stefan Kochanek

  2. Howard Hughes Medical Institute, One Baylor Plaza, Houston, Texas, 77030, USA

    Núria Morral & Arthur L. Beaudet

  3. Department of Biology and Pathology, McMaster University, Hamilton, Ontario, Canada, L8S 4K1

    Robin J. Parks & Frank L. Graham

  4. Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, 77030, USA

    Claire Langston

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Correspondence to Stefan Kochanek.

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Schiedner, G., Morral, N., Parks, R. et al. Genomic DNA transfer with a high-capacity adenovirus vector results in improved in vivo gene expression and decreased toxicity. Nat Genet 18, 180–183 (1998). https://doi.org/10.1038/ng0298-180

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