Yang Nan, Zhu Xiangying, Chen Lishan, Li Shenghua, Ren Daming
Institute of Genetics, Fudan University, Shanghai, PR China.
Cancer Biol Ther. 2008 Jan;7(1):145-51. doi: 10.4161/cbt.7.1.5195. Epub 2007 Oct 19.
RNAi has been successfully applied in genomic research, and it also holds considerable promise as a therapeutic approach to suppress disease-causing gene expression. Here, we show that attenuated S. typhimurium were capable of delivering shRNA-expressing vectors to mammalian cells and inducing RNAi in vitro and in vivo. Upon oral administration, S. typhimurium carrying shRNA-expressing vectors targeting bcl2 induced significant gene silencing in murine melanoma cells that led to a remarkably delayed tumor growth and prolonged survival in the mouse model. These results suggest that bacteria mediated RNAi may be a new potent approach to the treatment of cancers.
RNA干扰已成功应用于基因组研究，并且作为一种抑制致病基因表达的治疗方法也具有巨大潜力。在此，我们表明减毒鼠伤寒沙门氏菌能够将表达短发夹RNA的载体递送至哺乳动物细胞，并在体外和体内诱导RNA干扰。口服给药后，携带靶向bcl2的表达短发夹RNA载体的鼠伤寒沙门氏菌在小鼠黑色素瘤细胞中诱导了显著的基因沉默，导致小鼠模型中的肿瘤生长明显延迟且生存期延长。这些结果表明细菌介导的RNA干扰可能是一种治疗癌症的新的有效方法。
