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Development of human papillomavirus plasmids capable of episomal replication in human cell lines

Gene Therapy volume 6, pages 1317–1321 (1999)Cite this article

Abstract

Gene delivery into human cells has been facilitated by the development of viral vector systems. These vectors have shown great potential for the efficient delivery of therapeutic genes into human cells. A problem with many of the existing systems, however, is the integration of these vectors into the chromosome which affects the length of gene expression and may promote oncogenic transformation. In an effort to develop viral vectors that can replicate extrachromosomally in human cells, we have generated human papillomavirus (HPV) plasmids containing all the elements required for replication on a single DNA molecule. HPV plasmids containing the viral E1 and E2 genes (or the E1 gene alone) and an origin of replication were shown to replicate to significant levels in the transfected human cervical carcinoma C-33A cell line. Since approaches towards the possible gene therapy of cystic fibrosis (CF) are currently under intensive investigation, we have also tested short-term replication of HPV plasmids in the IB3 cell line derived from a CF patient. Our results demonstrate that HPV plasmids are capable of extrachromosomal replication in these cell lines and may potentially be important vectors for the delivery of therapeutic genes into human cells.

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Acknowledgements

We thank members of our laboratory for helpful discussions. This work was supported by grant GM51861 from the National Institutes of Health.

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Author notes

  1. F M Sverdrup

    Present address: Sequitur Inc, Waltham, 02453, MA, USA

Authors and Affiliations

  1. Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, 15261, PA, USA

    F M Sverdrup, L C Sheahan & S A Khan

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  1. F M Sverdrup
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  2. L C Sheahan
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  3. S A Khan
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Sverdrup, F., Sheahan, L. & Khan, S. Development of human papillomavirus plasmids capable of episomal replication in human cell lines. Gene Ther 6, 1317–1321 (1999). https://doi.org/10.1038/sj.gt.3300957

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