GENE THERAPY Eradication of neutralizing antibodies to factor VIII in canine hemophilia A after liver gene therapy
نویسندگان
چکیده
1Department of Hematology, The Children’s Hospital of Philadelphia, Philadelphia, PA; 2Department of Pathology and Molecular Medicine, Queen’s University, Kingston, ON; 3Department of Genetics, University of Pennsylvania, Philadelphia, PA; 4Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC; and 5Department of Pediatrics, University of Pennsylvania, Philadelphia, PA
منابع مشابه
Eradication of neutralizing antibodies to factor VIII in canine hemophilia A after liver gene therapy.
Inhibitory antibodies to factor VIII (FVIII) are a major complication in the treatment of hemophilia A, affecting approximately 20% to 30% of patients. Current treatment for inhibitors is based on long-term, daily injections of large amounts of FVIII protein. Liver-directed gene therapy has been used to induce antigen-specific tolerance, but there are no data in hemophilic animals with pre-exis...
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Hemophilia A, a deficiency of functional coagulation factor VIII (FVIII), is treated via protein replacement therapy. Restoring 1% to 5% of normal blood FVIII activity prevents spontaneous bleeding, making the disease an attractive gene therapy target. Previously, we have demonstrated short-term activity of a liver-specific AAV2 vector expressing canine B-domain-deleted FVIII (cFVIII) in a hemo...
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Background: Hemophilia B is an X-linked hereditary disorder of blood coagulation system which is caused by factor IX (FIX) deficiency. Factor IX is a plasma glycoprotein that participates in the coagulation process leading to the generation of fibrin. Replacement of factor IX with plasma-derived or recombinant factor IX is the conventional treatment for hemophilia B to raise the factor IX le...
متن کاملTherapeutic factor VIII levels and negligible toxicity in mouse and dog models of hemophilia A following gene therapy with high-capacity adenoviral vectors.
High-capacity adenoviral (HC-Ad) vectors expressing B-domain-deleted human or canine factor VIII from different liver-specific promoters were evaluated for gene therapy of hemophilia A. Intravenous administration of these vectors into hemophilic FVIII-deficient immunodeficient SCID mice (FVIIIKO-SCID) at a dose of 5 x 10(9) infectious units (IU) resulted in efficient hepatic gene delivery and l...
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Background and Objectives: Significant progress has been made in treatment of hemophilia. Ex-vivo gene therapy is going popular due to the capability of this method in using isogenic cells for genetic manipulation and reintroducing them into same host after proliferation. Most gene therapy techniques use viral vectors, which usually harbor a strong and non-specific promoter (e...
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تاریخ انتشار 2010