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Science 1 October 1993:
Vol. 262. no. 5130, pp. 117 - 119
DOI: 10.1126/science.8211118
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Articles

Science, Vol 262, Issue 5130, 117-119
Copyright © 1993 by American Association for the Advancement of Science

articles

In vivo gene therapy of hemophilia B: sustained partial correction in factor IX-deficient dogs

MA Kay, S Rothenberg, CN Landen, DA Bellinger, F Leland, C Toman, M Finegold, AR Thompson, MS Read, KM Brinkhous, and al. et

Department of Molecular Genetics, Baylor College of Medicine, Houston, TX 77030.

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.


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