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Hepatic gene therapy for haemophilia B
Author(s) -
Lee C. A.,
Kessler C. M.,
Varon D.,
Martinowitz U.,
Heim M.,
KAY M. A.
Publication year - 1998
Publication title -
haemophilia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.213
H-Index - 92
eISSN - 1365-2516
pISSN - 1351-8216
DOI - 10.1046/j.1365-2516.1998.440389.x
Subject(s) - factor ix , genetic enhancement , medicine , viral vector , clotting factor , vector (molecular biology) , immune system , haemophilia b , haemophilia , immunology , cancer research , virology , gene , recombinant dna , biology , haemophilia a , genetics , surgery
Summary. Early retroviral‐mediated factor IX gene transfer into deficient dogs showed that constitutive expression of low levels of factor IX which has led to persistent improvement of clinically relevant parameters such as the WBCT and PTT. Conversely, in vivo adenoviral mediated delivery of the factor IX cDNA into hepatocytes of haemophilia B dogs has resulted in greater than wild‐type plasma concentrations of clotting factor with complete, albeit transient normalization of haemostasis for a short time. An immune response directed against the vector transduced cells presented a big obstacle to clinical application. However, the future of gene therapy for factor IX deficiency appears bright with the development of fully adenoviral‐gene deleted vectors, rAAV and lentiviral vectors which seem to offer safety, therapeutic levels of factor IX and relatively long‐term persistence. We must proceed with cautious optimism as these vector systems undergo further scrutiny.