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Novel E2F decoy oligodeoxynucleotides inhibit in vitro vascular smooth muscle cell proliferation and in vivo neointimal hyperplasia

Gene Therapy volume 9, pages 1682–1692 (2002)Cite this article

Abstract

The transcription factor, E2F, plays a critical role in the trans-activation of several genes involved in cell cycle regulation. Previous studies showed that the transfection of cis element double-stranded decoy oligodeoxynucleotides (ODNs) corresponding to E2F binding sites inhibited the proliferation of vascular smooth muscle cells (VSMCs) and neointimal hyperplasia in injured vessels. We have developed a novel E2F decoy ODN with a circular dumbbell structure (CD-E2F) and compared its effects with those of the conventional phosphorothioated E2F decoy (PS-E2F) ODN. CD-E2F ODN was more stable than PS-E2F ODN, largely preserving its structural integrity after incubation in the presence of nucleases and sera. Moreover, CD-E2F ODN inhibited high glucose- and serum-induced transcriptional expression of cell cycle regulatory genes more strongly than PS-E2F ODN. Transfection of CD-E2F ODN resulted in more effective inhibition of VSMC proliferation in vitro and neointimal formation in vivo, compared with PS-E2F ODN. An approximately 40–50% lower dose of CD-E2F ODN than PS-E2F ODN was sufficient to attain similar effects. In conclusion, our results indicate that CD-E2F ODN may be a valuable tool in gene therapy protocols for inhibiting VSMC proliferation and studying transcriptional regulation.

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Acknowledgements

This study was supported by a grant from the Korea Health 21 R&D project, Ministry of Health & Welfare, Republic of Korea (HMP-99-M-08-0004 and 02-PJ-1-PG10-20708-0007)

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Authors and Affiliations

  1. Department of Microbiology, Kyungpook National University, Taegu, Korea

    J D Ahn & Y-H Kim

  2. Division of Gene Therapy Science, Osaka University Medical School, Osaka, Japan

    R Morishita & Y Kaneda

  3. Department of Internal Medicine, Keimyung University School of Medicine, Taegu, Korea

    H S Kim & I-K Lee

  4. Dongsan Kidney Institute, Keimyung University School of Medicine, Korea

    Y-C Chang

  5. Department of Internal Medicine, University of Ulsan School of Medicine, Seoul, Korea

    K-U Lee & J-Y Park

  6. Department of Internal Medicine, Yeungnam University School of Medicine, Taegu, Korea

    H W Lee

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Ahn, J., Morishita, R., Kaneda, Y. et al. Novel E2F decoy oligodeoxynucleotides inhibit in vitro vascular smooth muscle cell proliferation and in vivo neointimal hyperplasia. Gene Ther 9, 1682–1692 (2002). https://doi.org/10.1038/sj.gt.3301849

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  • DOI: https://doi.org/10.1038/sj.gt.3301849

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