Tumor vascular targeted delivery of polymer-conjugated adenovirus vector for cancer gene therapy
| Autor: | Yasuaki Kawai, Hiroyuki Mizuguchi, Naoki Okada, Yohei Mukai, Jian-Qing Gao, Yasuo Yoshioka, Shinsaku Nakagawa, Shogo Narimatsu, Yusuke Eto, Tomohiro Morishige, Xinglei Yao |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
endocrine system
Genes Viral Transgene Genetic enhancement animal diseases viruses Genetic Vectors Biology medicine.disease_cause Thymidine Kinase Viral vector Adenoviridae Polyethylene Glycols Mice Transduction Genetic Cell Line Tumor Drug Discovery Genetics medicine Animals Simplexvirus Transgenes Molecular Biology Pharmacology Regulation of gene expression Mice Inbred BALB C Gene Transfer Techniques virus diseases Genetic Therapy medicine.disease Primary tumor Molecular biology Vascular Neoplasms Mice Inbred C57BL Gene Expression Regulation Thymidine kinase Systemic administration Molecular Medicine Original Article |
| Zdroj: | Molecular therapy : the journal of the American Society of Gene Therapy. 19(9) |
| ISSN: | 1525-0024 |
| Popis: | Previously, we generated a cancer-specific gene therapy system using adenovirus vectors (Adv) conjugated to polyethylene glycol (Adv-PEG). Here, we developed a novel Adv that targets both tumor tissues and tumor vasculatures after systemic administration by conjugating CGKRK tumor vasculature homing peptide to the end of a 20-kDa PEG chain (Adv-PEG(CGKRK)). In a primary tumor model, systemic administration of Adv-PEG(CGKRK) resulted in ~500- and 100-fold higher transgene expression in tumor than that of unmodified Adv and Adv-PEG, respectively. In contrast, the transgene expression of Adv-PEG(CGKRK) in liver was about 400-fold lower than that of unmodified Adv, and was almost the same as that of Adv-PEG. We also demonstrated that transgene expression with Adv-PEG(CGKRK) was enhanced in tumor vessels. Systemic administration of Adv-PEG(CGKRK) expressing the herpes simplex virus thymidine kinase (HSVtk) gene (Adv-PEG(CGKRK)-HSVtk) showed superior antitumor effects against primary tumors and metastases with negligible side effects by both direct cytotoxic effects and inhibition of tumor angiogenesis. These results indicate that Adv-PEG(CGKRK) has potential as a prototype Adv with suitable efficacy and safety for systemic cancer gene therapy against both primary tumors and metastases. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|