Prospects for gene therapy of haemophilia

被引:40
作者
Nathwani, AC
Davidoff, AM
Tuddenham, EGD
机构
[1] UCL, Dept Haematol, London WC1E 6HX, England
[2] St Jude Childrens Res Hosp, Dept Surg, Memphis, TN 38105 USA
[3] Hammersmith Hosp, Imperial Coll, MRC Thrombosis & Haemostasis Res, London, England
关键词
gene therapy; haemophilia; insertional mutagenesis;
D O I
10.1111/j.1365-2516.2004.00926.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
That gene therapy offers the promise of a cure for haemophilia was apparent more than a decade ago. After years of failure, substantial progress in the efficiency of gene transfer technology has recently resulted in impressive success in animal models with haemophilia. However, fears of the risks intrinsic to such therapy have been raised by the fate of two children cured of immune deficiency by gene transfer who have, however, subsequently developed leukaemia as a result of insertional mutagenesis. The purpose of this review is to outline the current status of gene therapy in light of recent successes and tragedies and to consider the prospects for curing haemophilia in the short-to-medium term.
引用
收藏
页码:309 / 318
页数:10
相关论文
共 50 条
[31]   Extrachromosomal recombinant adeno-associated virus vector genomes are primarily responsible for stable liver transduction in vivo [J].
Nakai, H ;
Yant, SR ;
Storm, TA ;
Fuess, S ;
Meuse, L ;
Kay, MA .
JOURNAL OF VIROLOGY, 2001, 75 (15) :6969-6976
[32]   A limited number of transducible hepatocytes restricts a wide-range linear vector dose response in recombinant adeno-associated virus-mediated liver transduction [J].
Nakai, H ;
Thomas, CE ;
Storm, TA ;
Fuess, S ;
Powell, S ;
Wright, JF ;
Kay, MA .
JOURNAL OF VIROLOGY, 2002, 76 (22) :11343-11349
[33]   Adenovirus-mediated expression of the murine ecotropic receptor facilitates transduction of human hematopoietic cells with an ecotropic retroviral vector [J].
Nathwani, AC ;
Persons, DA ;
Stevenson, SC ;
Frare, P ;
McClelland, A ;
Nienhuis, AW ;
Vanin, EF .
GENE THERAPY, 1999, 6 (08) :1456-1468
[34]   Sustained high-level expression of human factor IX (hFIX) after liver-targeted delivery of recombinant adeno-associated virus encoding the hFIX gene in rhesus macaques [J].
Nathwani, AC ;
Davidoff, AM ;
Hanawa, H ;
Hu, YN ;
Hoffer, FA ;
Nikanorov, A ;
Slaughter, C ;
Ng, CYC ;
Zhou, JF ;
Lozier, JN ;
Mandrell, TD ;
Vanin, EF ;
Nienhuis, AW .
BLOOD, 2002, 100 (05) :1662-1669
[35]   Factors influencing in vivo transduction by recombinant adeno-associated viral vectors expressing the human factor IX cDNA [J].
Nathwani, AC ;
Davidoff, A ;
Hanawa, H ;
Zhou, JF ;
Vanin, EF ;
Nienhuis, AW .
BLOOD, 2001, 97 (05) :1258-1265
[36]   Therapeutic levels of human factor VIII and IX using HIV-1-based lentiviral vectors in mouse liver [J].
Park, F ;
Ohashi, K ;
Kay, MA .
BLOOD, 2000, 96 (03) :1173-1176
[37]   Phase 1 trial of FVIII gene transfer for severe hemophilia A using a retroviral construct administered by peripheral intravenous infusion [J].
Powell, JS ;
Ragni, MV ;
White, GC ;
Lusher, JM ;
Hillman-Wiseman, C ;
Moon, TE ;
Cole, V ;
Ramanathan-Girish, S ;
Roehl, H ;
Sajjadi, N ;
Jolly, DJ ;
Hurst, D .
BLOOD, 2003, 102 (06) :2038-2045
[38]  
Qiu XF, 1996, CHINESE MED J-PEKING, V109, P832
[39]   Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer [J].
Raper, SE ;
Chirmule, N ;
Lee, FS ;
Wivel, NA ;
Bagg, A ;
Gao, GP ;
Wilson, JM ;
Batshaw, ML .
MOLECULAR GENETICS AND METABOLISM, 2003, 80 (1-2) :148-158
[40]   Sustained human factor VIII expression in hemophilia a mice following systemic delivery of a gutless adenoviral vector [J].
Reddy, PS ;
Sakhuja, K ;
Ganesh, S ;
Yang, LJ ;
Kayda, D ;
Brann, T ;
Pattison, S ;
Golightly, D ;
Idamakanti, N ;
Pinkstaff, A ;
Kaloss, M ;
Barjot, C ;
Chamberlain, JS ;
Kaleko, M ;
Connelly, S .
MOLECULAR THERAPY, 2002, 5 (01) :63-73