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• W2165909566 abstract "Adenoviral vector-mediated gene therapy might have potential for long-term correction of the monogenic disease hemophilia A.In this study, we tested the efficacy of administering a helper-dependent adenoviral vector (HDV) designed for maximal liver-restricted canine factor VIII (cFVIII) expression on three out-bred hemophilia A dogs.Three FVIII-deficient animals from the University of North Carolina colony were injected with 1 x 10(12) (Dog A), and 3 x 10(12) (Dog B and C) vp kg(-1) helper-dependent adenoviral vector, and we performed systematic analysis of toxicity, persistence of therapeutic gene expression, and molecular analysis of gene transfer.We observed acute dose-dependent elevation in liver enzymes and thrombocytopenia after injection, although both were transient and resolved within 2 weeks. The whole blood clotting time (WBCT), plasma FVIII concentration, FVIII activity, and activated partial thromboplastin time in all animals improved significantly after treatment, and two animals receiving a higher dose reached near normal WBCT with low-level FVIII activity until terminal sacrifice at 3 months, and 2 years. Importantly, the treated dogs suffered no bleeding events after injection. Moreover, we observed persistent vector-specific DNA and RNA in liver tissue collected from one high-dose animal at days 18 and 79, and could not detect the formation of inhibitory antibodies.Although vector-associated toxicity remains an obstacle, a single injection of HDV led to long-term transgene expression and vector persistence in two FVIII-deficient animals with conversion of their severe phenotype to a moderate one." @default.
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• W2165909566 date "2006-06-01" @default.
• W2165909566 modified "2023-09-30" @default.
• W2165909566 title "Helper‐dependent adenoviral gene therapy mediates long‐term correction of the clotting defect in the canine hemophilia A model" @default.
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• W2165909566 doi "https://doi.org/10.1111/j.1538-7836.2006.01901.x" @default.
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