Zhang Jie, Ding Meng, Xu Kai, Mao Lijun, Zheng Junian
Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou, China.
Department of Urinary Surgery, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
Oncotarget. 2016 May 17;7(20):29824-34. doi: 10.18632/oncotarget.8035.
The small-interfering RNAs (siRNAs) have been employed to knockdown the expression of cancer-associated genes and shown some promise in cancer therapy. However, synthetic siRNA duplexes or plasmid mediated delivery of siRNAs have several problems, such as short half-life, low transfection efficiency and cytotoxicity associated with transfection. Conditionally replicating adenovirus (CRAds) as the delivery vector for short hairpin RNAs (shRNAs) could overcome these limitations and have shown augmented anti-tumor effects in experimental studies and preclinical trials. In this review, we summarize recent progress in the development of CRAds-shRNA for cancer treatment. Combination of CRAds-shRNA with chemotherapeutics, radiation, dendritic cells, monoclonal antibodies and small-molecule inhibitors will be necessary to eradicate cancer cells and cancer stem cells and achieve superior outcomes. The use of CRAd platform for efficient delivery of shRNAs and foreign genes will open a new avenue for cancer therapy.
小干扰RNA（siRNAs）已被用于敲低癌症相关基因的表达，并在癌症治疗中显示出一定的前景。然而，合成的siRNA双链体或质粒介导的siRNA递送存在一些问题，如半衰期短、转染效率低以及与转染相关的细胞毒性。条件性复制腺病毒（CRAds）作为短发夹RNA（shRNAs）的递送载体可以克服这些限制，并在实验研究和临床前试验中显示出增强的抗肿瘤作用。在本综述中，我们总结了用于癌症治疗的CRAds-shRNA开发的最新进展。将CRAds-shRNA与化疗药物、放疗、树突状细胞、单克隆抗体和小分子抑制剂联合使用对于根除癌细胞和癌症干细胞并取得更好的治疗效果是必要的。利用CRAd平台高效递送shRNAs和外源基因将为癌症治疗开辟一条新途径。
