Gene therapy as an adjuvant treatment for malignant gliomas: from bench to bedside

Malignant brain tumors, including high-grade gliomas, are among the most lethal of all cancers. Despite considerable advances, including multi-modality treatments with surgery, radiotherapy, and chemotherapy, the overall prognosis for patients with this disease remains dismal. Currently available treatments necessitate the development of more effective tumor-selective therapies. The use of gene therapy for brain tumor therapy is promising as it can be delivered in situ and selectively targets brain tumor cells while sparing the adjacent normal brain tissue. In this article, we summarize the laboratory and clinical work using viral, cell-based, and synthetic vectors, as well as other strategies focused on potentiate gene delivery. Although tangible results on patients’ survival remains to be further documented, significant advances in therapeutic gene transfer strategies have been made. The enthusiasm of this progress needs to be tempered by the realistic assessment of the challenges needed to be overcome. Finally, as the field of gene delivery progresses, advances must be made in identifying genes and proteins key to the treatment of malignant gliomas. Due to the great heterogeneity of malignant glioma cells, only approaches combining different strategies may be ultimately successful in defeating this disease.     

Survivin特异性siRNA真核表达载体的构建

目的构建Survivin特异性siRNA真核表达载体，为以Survivin基因为靶点、小干扰RNA（small interfering RNA，siRNA）为手段的白血病和其它恶性肿瘤基因治疗的基础和临床应用提供良好的技术手段。方法根据GeneBank数据库提供的Survivin基因所有变异体的共同核苷酸序列，按照Tuschl设计原则，选择设计双链siRNA，再转化为能表达其小发卡结构RNA（small hairpin RNA，shRNA）的DNA序列，并与载体pSINsi-hU6定向连接，构建受控于启动子u6的真核表达载体pSIN／shRNA1、pSIN／shR-NA2，经限制性内切酶酶切和DNA测序进行鉴定。结果构建Survivin特异性siRNA真核表达载体pSIN／shRNA1、pSIN／shRNA2，经限制性内切酶酶切和DNA测序证实与设计完全一致。结论Survivin特异性siRNA真核表达载体构建成功。