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Complete short-term correction of canine hemophilia A by in vivo gene
therapy
S Connelly, J Mount, A Mauser, JM Gardner, M Kaleko, A McClelland and CD Lothrop
Genetic Therapy Inc, Gaithersburg, MD, USA.
Hemophilia A is a severe bleeding disorder caused by a deficiency in
clotting factor VIII (FVIII). A canine model that closely mimics the human
disease was used to determine if an adenoviral vector expressing a human
FVIII cDNA could be used to correct the hemophilia A phenotype. Within 48
hours after peripheral vein administration of the vector to FVIII-deficient
dogs, the hemophilic phenotype was corrected, based on determination of the
activated clotting time, the activated partial thromboplastin time, and the
cuticle bleeding time. Direct measurement of human FVIII in the dog plasma
showed FVIII expression at amounts well above the human therapeutic level.
FVIII expression in treated dogs was short-term, lasting 1 to 2 weeks, due
to the development of a human FVIII-specific inhibitor antibody response.
These data provide the first demonstration of in vivo gene therapy of
hemophilia A.
Volume 88,
Issue 10,
pp. 3846-3853,
11/15/1996
Copyright © 1996 by The American Society of Hematology
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