title: Skeletal muscle-specific expression of human blood coagulation factor IX rescues factor IX deficiency mouse by AAV-mediated gene transfer.
abstract: The efficacy of recombinant adeno-associated virus (AAV) vector to deliver and express human blood clotting factor IX (hFIX) gene in skeletal muscle of coagulation factor IX deficiency mouse strain (FactorIX-knockout) is evaluated. The muscle creatine kinase enhancer (MCK) and beta-actin promoter (betaA) were used to drive the hFIX minigene (hFIXml), which was flanked by AAV inverted terminal repeats (ITRs). Following intramuscular injection of high titer (2.5 x 10(11) vector genomes/mL) of rAAV, increased hFIX expression (256 ng/mL of plasma) was achieved. The time course of hFIX expression demonstrated that the expression level gradually increased over a period of two weeks before anti-hFIX antibodies developed in mouse circulating plasma. Those results provided a promising evidence that rAAV-mediated gene transfer and skeletal muscle-specific expression of hFIX is a feasible strategy for treating patients for hemophilia B.
authors: Institute of Genetics, Fudan University, Shanghai, China.
authors: L
authors: L
authors: Lai
authors: L
authors: L
authors: Chen
authors: J
authors: J
authors: Wang
authors: H
authors: H
authors: Zhou
authors: D
authors: D
authors: Lu
authors: Q
authors: Q
authors: Wang
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authors: Gao
authors: X
authors: X
authors: Qiu
authors: J
authors: J
authors: Xue