期刊
BLOOD
卷 109, 期 4, 页码 1414-1421出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2006-03-010181
关键词
-
类别
资金
- MRC [G0502121] Funding Source: UKRI
- Medical Research Council [G0502121] Funding Source: researchfish
- Medical Research Council [G0502121] Funding Source: Medline
- NHLBI NIH HHS [HL073838, R01 HL073838] Funding Source: Medline
The safety and efficacy of peripheral venous administration of a self-complementary adeno-associated viral vector encoding the human FIX gene (scAAV-LP1-hFlXco) was evaluated in nonhuman primates for gene therapy of hemophilia B. Peripheral vein infusion of 1 X 10(12) vg/kg scAAV-LP1-hFIXco pseudotyped with serotype 8 capsid, in 3 macaques, resulted in stable therapeutic expression (more than 9 months) of human FIX (hFIX) at levels (1.1 +/- 0.5 mu g/mL, or 22% of normal) that were comparable to those achieved after direct delivery of the same vector dose into the portal circulation (1.3 +/- 0.3 mu g/mL, or 26% of normal). Importantly, the pattern of vector biodistribution after systemic and portal vein administration of scAAV-LP1-hFlXco was almost identical. Additionally, comparable levels of gene transfer were achieved in macaques with preexisting immunity to AAV8 following peripheral vein administration of 1 x 1012 vg/kg AAV5-pseudotyped scAAV-LP1-hFlXco. This confirms that alternative serotypes can circumvent preexisting naturally acquired immunity to AAV. Thus, peripheral venous administration of AAV5 and AAV8 vectors is safe and as effective at transducing the liver in nonhuman primates as direct vector administration into the portal circulation. These results should make vector administration to patients, especially those with a severe bleeding diathesis, significantly easier and safer.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据