Youn J-I, Park S-H, Jin H-T, Lee C-G, Seo S-H, Song M-Y, Lee C-W, Sung Y-C
1Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea.
Cancer Gene Ther. 2008 Nov;15(11):703-12. doi: 10.1038/cgt.2008.45. Epub 2008 Jul 4.
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.
蛋白质转导结构域（PTDs）是一类小肽，可促进多蛋白、DNA和病毒等大分子转导进入真核细胞。在此，我们证明，源自鲱鱼精蛋白的新型PTD（HP4）进入C6Bu1大鼠胶质瘤细胞系的速度似乎比其他已知的PTD（如Tat、Antp和Hph-1）更快。此外，HP4显著增强了重组腺病毒（rAds）体外转导至各种癌细胞系、间充质干细胞（MSCs）和树突状细胞的能力，这些细胞对rAd感染相对具有抗性。HP4将rAd递送至C6Bu1和MSCs的效率分别比Tat高20倍和7倍。在体外转导的小鼠结肠癌模型中，HP4增加编码IL-12N220L的rAd的表达与其抗肿瘤效果成正比。因此，这些结果表明，HP4可用于提高rAd的转导效率，从而增强rAd介导的基因治疗效果，特别是对于体外转导的细胞治疗。
