Journal Article

Adenovirus-Associated Virus Vector–Mediated Gene Transfer in Hemophilia B

Gray, John T, Nienhuis, Arthur W, Rangarajan, Savita, Spence, Yunyu, McIntosh, Jenny, Allay, James, High, Katherine A, Rosales, Cecilia, Glader, Bertil, Riddell, Anne, Mingozzi, Federico, Linch, David C, Sleep, Susan, Nathwani, Amit C, Davidoff, Andrew M, Reiss, Ulrike M, Kay, Mark A, O'Beirne, James, Cunningham, John M, Basner-Tschakarjan, Etiena, Srivastava, Deokumar, Harrington, Chris, Rustagi, Pradip, Pie, Arnulfo Jaquilmac, Coleman, John, Chowdary, Pratima, Pasi, John, Morton, Christopher L, Tuddenham, Edward G.D, Ng, Catherine Y.C, Smith, Keith, Zhou, Junfang

2011

Overview

Using techniques to target the liver, enhance gene expression, and avoid eliciting an immune response, the authors administered an adenovirus-associated virus containing the gene for factor IX (FIX) in six patients with hemophilia B. The result was either reduction or elimination of the need for FIX prophylaxis. Hemophilia B is an X-linked bleeding disorder that results from a defect in the gene encoding coagulation factor IX (FIX), a serine protease that is critical for blood clotting. Persons with severe hemophilia B have functional FIX levels that are less than 1% of normal values and have frequent bleeding episodes, which are associated with crippling arthropathy and early death. 1 , 2 Current treatment involves frequent intravenous injections of FIX protein concentrate (i.e., two to three times a week). However, this treatment is prophylactic rather than curative, is extremely expensive, and is associated with inhibitor formation. Somatic gene therapy for hemophilia . . .

• Publisher: Massachusetts Medical Society
• Subject: Adenoviruses / Adult / Biological and medical sciences / Coagulation factors / Dependovirus - genetics / Disease prevention / Factor IX - genetics / Factor IX - therapeutic use / Factor IX deficiency / Gene therapy / General aspects / Genetic Therapy - adverse effects / Genetic Vectors - immunology / Genomes / Glucocorticoids / Good Manufacturing Practice / Hematologic and hematopoietic diseases / Hemophilia / Hemophilia B - therapy / Hemorrhage / Hepatocytes / Humans / Immune clearance / Immunosuppressive agents / Infusions, Intravenous / Liver / Lymphocytes T / Medical research / Medical sciences / Methods / Middle Aged / Peripheral blood / Phenotypes / Platelet diseases and coagulopathies / Transgenes - immunology