Waddington, S.N. and Nivsarkar, M.S. and Mistry, A.R. and Buckley, S.M.K. and Kemball-Cook, G. and Mosley, K.L. and Mitrophanous, K. and Radcliffe, P. and Holder, M.V. and Brittan, M. and Georgiadis, A. and Al-Allaf, F. and Bigger, B.W. and Gregory, L.G. and Cook, H.T. and Ali, R.R. and Thrasher, A. and Tuddenham, E.D.G. and Themis, M. and Coutelle, C. (2004) Permanent phenotypic correction of hemophilia B in immunocompetent mice by prenatal gene therapy. Blood , 104 (9) pp. 2714-2721. 10.1182/blood-2004-02-0627.
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Hemophilia B, also known as Christmas disease, arises from mutations in the factor IX (F9) gene. Its treatment in humans, by recombinant protein substitution, is expensive, thus limiting its application to intermittent treatment in bleeding episodes and prophylaxis during surgery; development of inhibitory antibodies is an associated hazard. This study demonstrates permanent therapeutic correction of his disease without development of immune reactions by introduction of an HIV-based lentiviral vector encoding the human factor IX protein into the fetal circulation of immunocompetent hemophiliac and normal outbred mice. Plasma factor IX antigen remained at around 9%, 13%, and 16% of normal in the 3 hemophilia B mice, respectively, until the last measurement at 14 months. Substantial improvement in blood coagulability as measured by coagulation assay was seen in all 3 mice and they rapidly stopped bleeding after venipuncture. No humoral or cellular immunity against the protein, elevation of serum liver enzymes, or vector spread to the germline or maternal circulation were detected.
|Title:||Permanent phenotypic correction of hemophilia B in immunocompetent mice by prenatal gene therapy|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Wolfson Institute and Cancer Institute Administration > Cancer Institute > Research Department of Haematology|
UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Child Health > Department of Infection and Immunity > ICH - Molecular Immunology Unit
UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Child Health
UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
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