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Enhanced delivery efficiency of recombinant adenovirus into tumor and mesenchymal stem cells by a novel PTD

Cancer Gene Therapy volume 15, pages 703–712 (2008)Cite this article

Abstract

Protein transduction domains (PTDs) are small peptides that facilitate the transduction of large molecules such as polyproteins, DNA and viruses into a eukaryotic cell. Here, we demonstrated that a novel PTD (HP4) derived from herring protamine appeared to enter C6Bu1 rat glioma cell lines more rapidly than other known PTDs such as Tat, Antp and Hph-1. Moreover, HP4 significantly enhanced in vitro transduction of recombinant adenoviruses (rAds) into various cancer cell lines, mesenchymal stem cells (MSCs) and dendritic cells, which are relatively resistant to rAd infection. Enhancement of rAd delivery into C6Bu1 and MSCs by HP4 is 20 and 7 times higher than that by Tat, respectively. The increase in the expression of rAd encoding IL-12N220L by HP4 is proportional to its antitumor effect in the ex vivo transduced mouse colon cancer model. Thus, these results suggest that HP4 could be utilized to improve the transduction efficiency of rAd, resulting in enhanced efficacy of rAd-mediated gene therapy, especially for ex vivo-transduced cell therapy.

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Acknowledgements

We thank Dr Sang-Jun Ha for helpful discussion, Dr Yoon-Sun Yang for the human UCB-MSCs and Sang-Chun Lee and Kwan-Suk Lee for devoted animal care. This research was supported by Generic Technology Development Program, Minister of Commerce, Industry and Energy (10020817), Technology Innovation Development Program, SMEs (Small and Medium enterprises) (S0703222-C1449600-10000011), the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MOST) (no. M10534050001-08N3405-00110) and a grant from Biod, Korea.

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  1. J-I Youn and S-H Park: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea

    J-I Youn, S-H Park, S-H Seo, M-Y Song & Y-C Sung

  2. Research Institute, Genexine Co. Ltd, Seoul, Republic of Korea

    H-T Jin, C-G Lee & Y-C Sung

  3. Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea

    C-G Lee & C-W Lee

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Correspondence to Y-C Sung.

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Youn, JI., Park, SH., Jin, HT. et al. Enhanced delivery efficiency of recombinant adenovirus into tumor and mesenchymal stem cells by a novel PTD. Cancer Gene Ther 15, 703–712 (2008). https://doi.org/10.1038/cgt.2008.45

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