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Original

A comparative study of hFIX expression mediated by rAAV8 and rAAV1 administrated intramuscularly

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Pages 593-599 | Published online: 07 Jul 2009
 

Abstract

Background

Recombinant AAV serotype 8 (rAAV8) vector is relatively new for gene therapy. In this study, the hFIX expression mediated by rAAV8 injected intramuscularly was compared with that by rAAV1.

Methods

rAAV8-hFIX or rAAV1-hFIX viruses were injected intramuscularly into two hind limbs of mice at doses of 5×1010 gc and 2.5×1012 gc (genome copy). The hFIX expression in the mouse plasma was detected by ELISA, APTT and Western blotting. The virus distribution was analyzed by immunohistochemical assay.

Results

When the mice were infected with 5×1010 gc virus, high levels of hFIX in the plasma of five rAAV8-hFIX virus-infected mice were detected 2 weeks after injection. A hFIX peak above 5000 ng/mL appeared between 2 and 6 weeks after injection. Relatively low levels of hFIX were detected in the plasma of rAAV1-hFIX virus-infected mice 2 weeks after injection. An hFIX peak above 3000 ng/mL appeared between 4 and 10 weeks after injection. However, much lower levels of hFIX were detected in mice infected with higher dose of rAAV8 virus. The hFIX in the mouse plasma was active biologically. The viruses were distributed mainly in the muscles of hind limbs.

Discussion

Gene expression mediated by rAAV8 was sooner and stronger than that by rAAV1 after intramuscular administration. Inhibition might have been triggered markedly by rAAV8 at high doses.

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