Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, China.
Curr Cancer Drug Targets. 2011 Sep;11(7):810-25. doi: 10.2174/156800911796798896.
Adenovirus vectors (Adv) are the most frequently used vectors in gene therapy research, especially in cancer gene therapy. However, despite encouraging preclinical and early clinical results, the successful clinical utility of gene therapy has not yet been fully realized. Challenges to clinical trial success for targeted Adv include inefficient Adv-mediated gene transfer (because many tumor cells lack Adv receptors), poor transduction in tumor tissues after systemic administration, accumulation and undesirable transgene expression in the liver. This review summarizes current targeting strategies for Adv to overcome these obstacles. Strategies include transductional selectivity through genetic modification of viral coat proteins, transcriptional selectivity by means of tumor-specific promoters, and selective biodistribution from conjugation with targeting ligands or polymers such as polyethylene glycol (PEG). Furthermore, combining selective biodistribution and active targeting ligands such as proteins, antibodies and peptides is an intriguing and promising approach that will also be covered in this review. These studies have provided new insights into our understanding of the utility of Adv in cancer gene therapy.
腺病毒载体（Adv）是基因治疗研究中最常使用的载体，特别是在癌症基因治疗中。然而，尽管临床前和早期临床研究结果令人鼓舞，但基因治疗的成功临床应用尚未完全实现。针对靶向 Adv 的临床试验成功面临的挑战包括：Adv 介导的基因转移效率低下（因为许多肿瘤细胞缺乏 Adv 受体）、全身给药后肿瘤组织中的转导不良、在肝脏中积累和不理想的转基因表达。本综述总结了目前用于 Adv 的靶向策略，以克服这些障碍。策略包括通过病毒衣壳蛋白的遗传修饰实现转导选择性、通过肿瘤特异性启动子实现转录选择性，以及通过与靶向配体或聚合物（如聚乙二醇（PEG））缀合实现选择性生物分布。此外，结合选择性生物分布和主动靶向配体，如蛋白质、抗体和肽，也是一种有趣且有前途的方法，这也将在本综述中讨论。这些研究为我们理解 Adv 在癌症基因治疗中的应用提供了新的见解。
