Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering and Artificial Cells and Organs Research Centre, Faculty of Medicine, McGill University, 3775 University Street, Montreal, QC H3A 2B4, Canada.
Mol Biotechnol. 2010 Jun;45(2):129-39. doi: 10.1007/s12033-010-9248-7.
Present therapeutic strategies for most cancers are restricted mainly to the primary tumors and are also not very effective in controlling metastatic states. Alternatively, gene therapy can be a potential option for treating such cancers. Currently mammalian viral-based cancer gene therapy is the most popular approach, but the efficacy has been shown to be quite low in clinical trials. In this study, for the first time, the insect cell-specific baculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV) has been evaluated as a vector for gene delivery to colorectal cancer cells. Experiments involving factorial design were employed to study the individual and combined effects of different parameters such as multiplicity of infection (MOI), viral incubation time and epigenetic factors on transduction efficiency. The results demonstrate that baculovirus gene delivery system holds immense potential for development of a new generation of highly effective virotherapy for colorectal, as well as other major carcinomas (breast, pancreas, and brain), and offers significant benefits to traditional animal virus-based vectors with respect to safety concerns.
目前,大多数癌症的治疗策略主要局限于原发性肿瘤,并且在控制转移性肿瘤方面也不是非常有效。相比之下,基因治疗可能是治疗此类癌症的一种潜在选择。目前,基于哺乳动物病毒的癌症基因治疗是最受欢迎的方法,但临床试验表明其疗效相当低。在这项研究中,杆状病毒 Autographa californica 多角体病毒(AcMNPV)首次被评估为一种将基因递送至结直肠癌细胞的载体。实验采用析因设计来研究不同参数(如感染复数(MOI)、病毒孵育时间和表观遗传因素)的单独和联合效应对转导效率的影响。结果表明,杆状病毒基因传递系统为开发新一代高效结直肠病毒疗法,以及其他主要癌症(乳腺癌、胰腺癌和脑癌)提供了巨大的潜力,并相对于传统的基于动物病毒的载体在安全性方面具有显著优势。