title: In vivo gene therapy of hemophilia B: sustained partial correction in factor IX-deficient dogs.
abstract: The liver represents a model organ for gene therapy. A method has been developed for hepatic gene transfer in vivo by the direct infusion of recombinant retroviral vectors into the portal vasculature, which results in the persistent expression of exogenous genes. To determine if these technologies are applicable for the treatment of hemophilia B patients, preclinical efficacy studies were done in a hemophilia B dog model. When the canine factor IX complementary DNA was transduced directly into the hepatocytes of affected dogs in vivo, the animals constitutively expressed low levels of canine factor IX for more than 5 months. Persistent expression of the clotting factor resulted in reductions of whole blood clotting and partial thromboplastin times of the treated animals. Thus, long-term treatment of hemophilia B patients may be feasible by direct hepatic gene therapy in vivo.
authors.affiliation: Department of Molecular Genetics, Baylor College of Medicine, Houston, TX 77030.
authors.forename: M A
authors.initials: MA
authors.lastname: Kay
authors.forename: S
authors.initials: S
authors.lastname: Rothenberg
authors.forename: C N
authors.initials: CN
authors.lastname: Landen
authors.forename: D A
authors.initials: DA
authors.lastname: Bellinger
authors.forename: F
authors.initials: F
authors.lastname: Leland
authors.forename: C
authors.initials: C
authors.lastname: Toman
authors.forename: M
authors.initials: M
authors.lastname: Finegold
authors.forename: A R
authors.initials: AR
authors.lastname: Thompson
authors.forename: M S
authors.initials: MS
authors.lastname: Read
authors.forename: K M
authors.initials: KM
authors.lastname: Brinkhous
mesh_terms: D000818:Animals; D002460:Cell Line; D004285:Dogs; D005164:Factor IX / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D002836:Hemophilia B / Q000097:blood / Q000235:genetics / Q000628:therapy*; D006498:Hepatectomy; D008099:Liver / Q000378:metabolism*; D010314:Partial Thromboplastin Time; D012190:Retroviridae / Q000235:genetics; D014914:Whole Blood Coagulation Time
chemical_list: D005164:Factor IX