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CRISPR/Cas9-mediated somatic correction of a novel coagulator factor IX gene mutation ameliorates hemophilia in mouse 期刊论文

编号：

77762a66-f5da-44fc-9660-0189501d61ed
作者：

Guan, Yuting#^[1,2]Ma, Yanlin#*^[3,4]Li, Qi^[3];Sun, Zhenliang^[5]Ma, Lie^[1,2];Wu, Lijuan^[1,2];Wang, Liren^[1,2];Zeng, Li^[1,2];Shao, Yanjiao^[1,2];Chen, Yuting^[1,2];Ma, Ning^[3];Lu, Wenqing^[1,2];Hu, Kewen^[1,2];Han, Honghui^[6];Yu, Yanhong^[4];Huang, Yuanhua^[3];Liu, Mingyao*^[1,2,7]Li, Dali*^[1,2]
语种：

英文
期刊：

EMBO MOLECULAR MEDICINE ISSN：1757-4676 2016 年 8 卷 5 期 (477 - 488) ; MAY
收录：
关键词：

gene therapy genome editing hemophilia B hemostasis monogenetic disease
摘要：

The X-linked genetic bleeding disorder caused by deficiency of coagulator factor IX, hemophilia B, is a disease ideally suited for gene therapy with genome editing technology. Here, we identify a family with hemophilia B carrying a novel mutation, Y371D, in the human F9 gene. The CRISPR/Cas9 system was used to generate distinct genetically modified mouse models and confirmed that the novel Y371D mutation resulted in a more severe hemophilia B phenotype than the previously identified Y371S mutation. To develop therapeutic strategies targeting this mutation, we subsequently compared naked DNA constructs versus adenoviral vectors to deliver Cas9 components targeting the F9 Y371D mutation in adult mice. After treatment, hemophilia B mice receiving naked DNA constructs exhibited correction of over 0.56% of F9 alleles in hepatocytes, which was sufficient to restore hemostasis. In contrast, the adenoviral delivery system resulted in a higher corrective efficiency but no therapeutic effects due to severe hepatic toxicity. Our studies suggest that CRISPR/Cas-mediated insitu genome editing could be a feasible therapeutic strategy for human hereditary diseases, although an efficient and clinically relevant delivery system is required for further clinical studies.
推荐引用方式
GB/T 7714：

Guan Yuting,Ma Yanlin,Li Qi, et al. CRISPR/Cas9-mediated somatic correction of a novel coagulator factor IX gene mutation ameliorates hemophilia in mouse [J].EMBO MOLECULAR MEDICINE,2016,8(5):477-488.
APA：

Guan Yuting,Ma Yanlin,Li Qi,Sun Zhenliang,&Li Dali.(2016).CRISPR/Cas9-mediated somatic correction of a novel coagulator factor IX gene mutation ameliorates hemophilia in mouse .EMBO MOLECULAR MEDICINE,8(5):477-488.
MLA：

Guan Yuting, et al. "CRISPR/Cas9-mediated somatic correction of a novel coagulator factor IX gene mutation ameliorates hemophilia in mouse" .EMBO MOLECULAR MEDICINE 8,5(2016):477-488.
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