Safe and efficient transduction of the liver after peripheral vein infusion of self-complementary AAV vector results in stable therapeutic expression of human FIX in nonhuman primates

作者: Amit C. Nathwani , John T. Gray , Jenny McIntosh , Catherine Y. C. Ng , Junfang Zhou

DOI: 10.1182/BLOOD-2006-03-010181

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摘要: The safety and efficacy of peripheral venous administration a self-complementary adeno-associated viral vector encoding the human FIX gene (scAAV-LP1-hFIXco) was evaluated in nonhuman primates for therapy hemophilia B. Peripheral vein infusion 1 x 1012 vg/kg scAAV-LP1-hFIXco pseudotyped with serotype 8 capsid, 3 macaques, resulted stable therapeutic expression (more than 9 months) (hFIX) at levels (1.1 ± 0.5 µg/mL, or 22% normal) that were comparable to those achieved after direct delivery same dose into portal circulation (1.3 0.3 26% normal). Importantly, pattern biodistribution systemic almost identical. Additionally, transfer macaques preexisting immunity AAV8 following AAV5-pseudotyped scAAV-LP1-hFIXco. This confirms alternative serotypes can circumvent naturally acquired AAV. Thus, AAV5 vectors is safe as effective transducing liver circulation. These results should make patients, especially severe bleeding diathesis, significantly easier safer.

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