Gene Therapy for Hemophilia

被引:68
作者
Nienhuis, Arthur W. [1 ]
Nathwani, Amit C. [2 ]
Davidoff, Andrew M. [3 ]
机构
[1] St Jude Childrens Res Hosp, Dept Hematol, Div Expt Hematol, MS 341, Memphis, TN 38105 USA
[2] UCL, Canc Inst, Dept Hematol, 72 Huntley St, London WC1E 6BT, England
[3] St Jude Childrens Res Hosp, Dept Surg, Memphis, TN 38105 USA
关键词
ADENOASSOCIATED VIRAL VECTORS; FACTOR-IX EXPRESSION; HIGHLY EFFICIENT TRANSDUCTION; NONHUMAN PRIMATE LIVER; OF-THE-ART; IN-VIVO; AAV VECTOR; VIRUS VECTORS; FACTOR-VIII; HUMAN HEPATOCYTES;
D O I
10.1016/j.ymthe.2017.03.033
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
The X-linked bleeding disorder hemophilia causes frequent and exaggerated bleeding that can be life-threatening if untreated. Conventional therapy requires frequent intravenous infusions of the missing coagulation protein (factor VIII [ FVIII] for hemophilia A and factor IX [FIX] for hemophilia B). However, a lasting cure through gene therapy has long been sought. After a series of successes in small and large animal models, this goal has finally been achieved in humans by in vivo gene transfer to the liver using adeno-associated viral (AAV) vectors. In fact, multiple recent clinical trials have shown therapeutic, and in some cases curative, expression. At the same time, cellular immune responses against the virus have emerged as an obstacle in humans, potentially resulting in loss of expression. Transient immune suppression protocols have been developed to blunt these responses. Here, we provide an overview of the clinical development of AAV gene transfer for hemophilia, as well as an outlook on future directions.
引用
收藏
页码:1163 / 1167
页数:5
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