Muscle injection of rAAV/mFIX to secrete clotting factor IX corrects the hemorrhagic tendencies in hemophilia B mice |
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| Affiliation: | 1. State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, China
2. State Key Laboratory of Molecular Virology and Genetic Engineering, Institute of Virology, Chinese Academy of Preventive Medicine, Beijing 100052, China |
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| Abstract: | Recombinant AAV particles of high titer (>1013 virus genome/mL) were prepared according to the rHSV/AAV helper virus method. After intramuscular injection of viral vectors in the hind limb, a sustained elevated level (>370 ng/mL) of murine FIX expression in the plasma of hemophilia B mouse was detected and persisted for more than 350 days. The biological activity reached 30% of normal levels, and bleeding symptoms in the treated mice were significantly alleviated. No anti-FIX antibody (inhibitor) was detected, though anti-AAV antibodies were found at a very low level after single injection. Repeated injection with rAAV/mFIX led to a variation in anti-AAV antibody levels between the two groups which had received different doses. Results from tissue analysis confirmed the skeletal muscle as the origin for circulating functional mFIX. Our results suggest that AAV-mediated gene transfer offers a promising method of gene therapy for hemophilia B. |
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| Keywords: | hemophilia B mouse gene therapy AAV HSV |
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