Liver-directed lentiviral gene therapy in a dog model of hemophilia B
Liver-directed lentiviral gene therapy in a dog model of hemophilia B
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DOI：
10.1126/scitranslmed.aaa1405
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发表时间：
2015-03-04
影响因子：
17.1
通讯作者：
Naldini, Luigi
中科院分区：
文献类型：
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作者：
Cantore, Alessio;Ranzani, Marco;Naldini, Luigi
我们在血友病B的大型动物模型中研究了使用慢病毒载体的肝脏定向基因治疗的疗效，并评估了在肿瘤易感小鼠模型中插入突变的风险。我们发现，使用慢病毒载体靶向表达犬凝血因子IX转基因肝细胞的基因治疗耐受性良好，并提供了一个稳定的长期生产凝血因子IX的狗与血友病B。通过利用三种不同的小鼠模型来扩增插入突变的结果，我们发现这些慢病毒载体没有检测到遗传毒性。我们的研究结果表明，慢病毒载体可能是一个有吸引力的候选人，针对肝脏的基因治疗，并可能是潜在的有用的血友病的治疗。
We investigated the efficacy of liver-directed gene therapy using lentiviral vectors in a large animal model of hemophilia B and evaluated the risk of insertional mutagenesis in tumor-prone mouse models. We showed that gene therapy using lentiviral vectors targeting the expression of a canine factor IX transgene in hepatocytes was well tolerated and provided a stable long-term production of coagulation factor IX in dogs with hemophilia B. By exploiting three different mouse models designed to amplify the consequences of insertional mutagenesis, we showed that no genotoxicity was detected with these lentiviral vectors. Our findings suggest that lentiviral vectors may be an attractive candidate for gene therapy targeted to the liver and may be potentially useful for the treatment of hemophilia.