Vassaux Georges, Nitcheu Josianne, Jezzard Sarah, Lemoine Nick R
Cancer Research UK Molecular Oncology Unit, Barts and The London School of Medicine and Dentistry, John Vane Science Centre, Charterhouse Square, UK.
J Pathol. 2006 Jan;208(2):290-8. doi: 10.1002/path.1865.
The ability of bacteria to mediate gene transfer has only recently been established and these observations have led to the utilization of various bacterial strains in gene therapy. The types of bacteria used include attenuated strains of Salmonella, Shigella, Listeria, and Yersinia, as well as non-pathogenic Escherichia coli. For some of these vectors, the mechanism of DNA transfer from the bacteria to the mammalian cell is not yet fully understood but their potential to deliver therapeutic molecules has been demonstrated in vitro and in vivo in experimental models. Therapeutic benefits have been observed in vaccination against infectious diseases, immunotherapy against cancer, and topical delivery of immunomodulatory cytokines in inflammatory bowel disease. In the case of attenuated Salmonella, used as a tumour-targeting vector, clinical trials in humans have demonstrated the proof of principle but they have also highlighted the need for the generation of strains with reduced toxicities and improved colonization properties. Altogether, the encouraging results obtained in the studies presented in this review justify further development of bacteria as a therapeutic vector against many types of pathology.
细菌介导基因转移的能力直到最近才被证实，这些观察结果促使人们在基因治疗中利用各种菌株。所使用的细菌类型包括减毒的沙门氏菌、志贺氏菌、李斯特菌和耶尔森氏菌菌株，以及非致病性大肠杆菌。对于其中一些载体，DNA从细菌转移到哺乳动物细胞的机制尚未完全了解，但它们在实验模型的体外和体内均已证明具有递送治疗分子的潜力。在针对传染病的疫苗接种、针对癌症的免疫疗法以及在炎症性肠病中局部递送免疫调节细胞因子方面均观察到了治疗益处。以减毒沙门氏菌作为肿瘤靶向载体为例，人体临床试验已证明了其原理，但也凸显了生成毒性更低、定植特性更好的菌株的必要性。总之，本综述中研究所获得的令人鼓舞的结果证明，进一步开发细菌作为针对多种病理类型的治疗载体是合理的。
