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Permanent phenotypic correction of hemophilia B in immunocompetent mice by prenatal gene therapy

Waddington, S.N.; Nivsarkar, M.S.; Mistry, A.R.; Buckley, S.M.K.; Kemball-Cook, G.; Mosley, K.L.; ... Coutelle, C.; + view all (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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Abstract

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.

Type:Article
Title:Permanent phenotypic correction of hemophilia B in immunocompetent mice by prenatal gene therapy
DOI:10.1182/blood-2004-02-0627
Publisher version:http://dx.doi.org/10.1182/blood-2004-02-0627
Language:English
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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