Journal
CANCER GENE THERAPY
Volume 15, Issue 11, Pages 703-712Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/cgt.2008.45
Keywords
protein transduction domains; HP4; recombinant adenovirus
Categories
Funding
- Generic Technology Development Program
- Minister of Commerce, Industry and Energy [10020817]
- Technology Innovation Development Program
- SMEs (Small and Medium enterprises) [S0703222-C1449600-10000011]
- Korea Science and Engineering Foundation (KOSEF)
- Korea government (MOST) [M10534050001-08N3405-00110]
- Biod, Korea
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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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