血友病A的基因治疗

中国临床药理学与治疗学 ›› 2010, Vol. 15 ›› Issue (8): 932-937.

血友病A的基因治疗

刘慕君, 刘艳平, 刘雄昊

中南大学生物科学与技术学院,长沙 410013,湖南

收稿日期:2010-03-11 修回日期:2010-04-24 出版日期:2010-08-26 发布日期:2020-09-17
通讯作者: 刘雄昊,男,博士,副教授,研究方向:基因治疗。E-mail:liuxionghao@sklmg.edu.cn
作者简介:刘慕君,博士,讲师, 研究方向:基因治疗。E-mail: liumujun@sklmg.edu.cn
基金资助:
国家自然科学基金资助项目(30700458;30900801)

Gene therapy for hemophilia A

LIU Mo-jun, LIU Yan-ping, LIU Xiong-hao

College of Biological Science and Technology, Central South University, Changsha 410013, Hunan, China

Received:2010-03-11 Revised:2010-04-24 Online:2010-08-26 Published:2020-09-17

摘要/Abstract

摘要： 血友病A是一种X-连锁隐性遗传病,在男性中的发病率约为(1~2)/10000。血友病A的临床症状主要是自发性关节、软组织或其他组织的出血、血肿,常可致残,甚至危及生命。其致病机制是由于编码凝血因子Ⅷ的基因先天性异常而导致的凝血因子Ⅷ缺乏或功能缺陷。血友病A是基因治疗的首选疾病之一。本文就血友病A基因治疗中所采用的载体和靶细胞作一综述。

关键词: 人凝血因子Ⅷ, 血友病A, 基因治疗

Abstract: Hemophilia A is an X chromosome-linked recessive inheritable bleeding disorder with an estimated incidence of 1-2 per 10000 males. Patients with Hemophilia A experience spontaneous bleeding into joints, soft tissues and other sites. Uncontrolled haemorrhagic episodes are crippling and potentially life threatening. Hemophilia A is caused by a deficiency or abnormality in factor Ⅷ, which is one of the most attractive candidates for gene therapy. In this article, the research of vectors and target cell in gene therapy for hemophilia A was reviewed.

Key words: hFⅧ, Hemophilia A, Gene therapy

中图分类号:

R554⁺.1

刘慕君, 刘艳平, 刘雄昊. 血友病A的基因治疗[J]. 中国临床药理学与治疗学, 2010, 15(8): 932-937.

LIU Mo-jun, LIU Yan-ping, LIU Xiong-hao. Gene therapy for hemophilia A[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(8): 932-937.

参考文献

[1] Tripodi A. Levels of coagulation factors and venous thromboembolism[J]. Haematologica, 2003,88(6): 705-711.
[2] Moayeri M, Ramezani A, Morgan RA, et al. Sustained phenotypic correction of hemophilia a mice following oncoretroviral-mediated expression of a bioengineered human factor VIII gene in long-term hematopoietic repopulating cells[J]. Mol Ther, 2004, 10(5): 892-902.
[3] Van Damme A, Chuah MK, Dell'accio F, et al. Bone marrow mesenchymal cells for haemophilia A gene therapy using retroviral vectors with modified long-terminal repeats[J]. Haemophilia, 2003,9(1): 94-103.
[4] Herder C, Tonn T, Oostendorp R, et al. Sustained expansion and transgene expression of coagulation factor VIII-transduced cord blood-derived endothelial progenitor cells[J]. Arterioscler Thromb Vasc Biol, 2003, 23(12): 2266-2272.
[5] Andrews JL, Weaver L, Kaleko M, et al. Efficient adenoviral vector transduction and expression of functional human factor VIII in cultured primary human hepatocytes[J]. Haemophilia, 1999, 5(3): 160-168.
[6] Andrews JL, Kadan MJ, Gorziglia MI, et al. Generation and characterization of E1/E2a/E3/E4-deficient adenoviral vectors encoding human factor VIII[J]. Mol Ther, 2001, 3(3): 329-336.
[7] Chao H, Mao L, Bruce AT, et al. Sustained expression of therapeutic levels of human factor VIII in mice[J]. Blood, 1996, 87(11): 4671-4677.
[8] Chuah MK, Schiedner G, Thorrez L, et al. Therapeutic factor VIII levels and negligible toxicity in mouse and dog models of hemophilia A following gene therapy with high-capacity adenoviral vectors[J]. Blood, 2003, 101(5): 1734-1743.
[9] Schmidt M, Voutetakis A, Afione S, et al. Adeno-associated virus type 12 (AAV12): a novel AAV serotype with sialic acid- and heparan sulfate proteoglycan-independent transduction activity[J]. J Virol, 2008, 82(3): 1399-406.
[10] Gnatenko DV, Saenko EL, Jesty J, et al.Human factor VIII can be packaged and functionally expressed in an adeno-associated virus background: applicability to haemophilia A gene therapy[J]. Br J Haematol, 1999, 104(1): 27-36.
[11] Sarkar R, Xiao W, Kazazian HH Jr. A single adeno-associated virus (AAV)-murine factor VIII vector partially corrects the hemophilia A phenotype[J]. J Thromb Haemost, 2003, 1(2): 220-226.
[12] Jiang H, Lillicrap D, Patarroyo-White S, et al. Multiyear therapeutic benefit of AAV serotypes 2, 6, and 8 delivering factor VIII to hemophilia A mice and dogs[J]. Blood, 2006, 108(1): 107-115.
[13] Burton M, Nakai H, Colosi P, et al. Coexpression of factor VIII heavy and light chain adeno-associated viral vectors produces biologically active protein[J]. Proc Natl Acad Sci USA, 1999, 96(22): 12725-12730.
[14] Chen L, Zhu F, Li J, et al. The enhancing effects of the light chain on heavy chain secretion in split delivery of factor VIII gene[J]. Mol Ther, 2007,15(10): 1856-1862.
[15] Liu F, Song Y, Liu D. Hydrodynamics-based transfection in animals by systemic administration of plasmid DNA[J]. Gene Ther, 1999, 6(7): 1258-1266.
[16] Zhang G, Budker V, Wolff JA. High levels of foreign gene expression in hepatocytes after tail vein injections of naked plasmid DNA[J]. Hum Gene Ther, 1999, 10(10): 1735-1737.
[17] Herweijer H, Zhang G, Subbotin VM, et al. Time course of gene expression after plasmid DNA gene transfer to the liver[J]. J Gene Med, 2001, 3(3): 280-291.
[18] Ye P, Thompson AR, Sarkar R, et al. Naked DNA transfer of Factor VIII induced transgene-specific, species-independent immune response in hemophilia A mice[J]. Mol Ther, 2004, 10(1): 117-126.
[19] Turgeman G, Pittman DD, Müller R, et al. Engineered human mesenchymal stem cells: a novel platform for skeletal cell mediated gene therapy[J]. J Gene Med, 2001, 3(3): 240-251.
[20] Roth DA, Tawa NE Jr, O'Brien JM, et al. Nonviral transfer of the gene encoding coagulation factor VIII in patients with severe hemophilia A[J]. N Engl J Med, 2001, 344(23): 1735-1742.
[21] Lin Y, Chang L, Solovey A, et al. Use of blood outgrowth endothelial cells for gene therapy for hemophilia A[J]. Blood, 2002, 99(2): 457-462.
[22] Mátrai J, Chuah MK, VandenDriessche T. Preclinical and clinical progress in hemophilia gene therapy[J]. Curr Opin Hematol, 2010, 17(5):387-392.
[23] Ohlfest JR, Frandsen JL, Fritz S, et al. Phenotypic correction and long-term expression of factor VIII in hemophilic mice by immunotolerization and nonviral gene transfer using the Sleeping Beauty transposon system[J]. Blood, 2005, 105(7): 2691-2698.
[24] Chao H, Mansfield SG, Bartel RC, et al. Phenotype correction of hemophilia A mice by spliceosome-mediated RNA trans-splicing[J]. Nat Med, 2003, 9(8): 1015-1019.
[25] 郭建友, 霍海如, 姜廷良, 内皮细胞功能及其异质性研究的进展[J]. 中国临床药理学与治疗学, 2005, 10(10): 1081-1085.
[26] Rosenberg JB, Greengard JS, Montgomery RR. Genetic induction of a releasable pool of factor VIII in human endothelial cells[J]. Arterioscler Thromb Vasc Biol, 2000,20(12):2689-2695.
[27] Matsui H, Shibata M, Brown B, et al. Ex vivo gene therapy for hemophilia A that enhances safe delivery and sustained in vivo factor VIII expression from lentivirally engineered endothelial progenitors[J]. Stem Cells, 2007, 25(10): 2660-2669.
[28] Ide LM, Gangadharan B, Chiang KY, et al. Hematopoietic stem-cell gene therapy of hemophilia A incorporating a porcine factor VIII transgene and nonmyeloablative conditioning regimens[J]. Blood, 2007, 110(8): 2855-2863.
[29] Jeon HJ, Oh TK, Kim OH, et al. Delivery of factor VIII gene into skeletal muscle cells using lentiviral vector[J]. Yonsei Med J, 2010,51(1): 52-57.