Tumor Vascular Targeted Delivery of Polymer-conjugated Adenovirus Vector for Cancer Gene Therapy
作者： Xinglei Yao , Yasuo Yoshioka , Tomohiro Morishige , Yusuke Eto , Shogo Narimatsu
DOI: 10.1038/MT.2011.112
关键词: Thymidine kinase 、 Transgene 、 Biology 、 Molecular biology 、 Systemic administration 、 Adenoviridae 、 Primary tumor 、 Regulation of gene expression 、 Genetic enhancement 、 Viral vector
摘要: Previously, we generated a cancer-specific gene therapy system using adenovirus vectors (Adv) conjugated to polyethylene glycol (Adv-PEG). Here, developed novel Adv that targets both tumor tissues and vasculatures after systemic administration by conjugating CGKRK vasculature homing peptide the end of 20-kDa PEG chain (Adv-PEGCGKRK). In primary model, Adv-PEGCGKRK resulted in ~500- 100-fold higher transgene expression than unmodified Adv-PEG, respectively. contrast, liver was about 400-fold lower Adv, almost same as Adv-PEG. We also demonstrated with enhanced vessels. Systemic expressing herpes simplex virus thymidine kinase (HSVtk) (Adv-PEGCGKRK-HSVtk) showed superior antitumor effects against tumors metastases negligible side direct cytotoxic inhibition angiogenesis. These results indicate has potential prototype suitable efficacy safety for cancer metastases.
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