期刊
HUMAN GENE THERAPY
卷 12, 期 5, 页码 563-573出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/104303401300042500
关键词
-
资金
- NIDDK NIH HHS [K02 DK02575, R01 DK48028, R21 DK53920] Funding Source: Medline
Although AAV vectors show promise for hepatic gene therapy, the optimal transcriptional regulatory elements have not yet been identified. In this study, we show that an AAV vector with the CMV enhancer/chicken beta -actin promoter results in 9.5-fold higher expression after portal vein injection than an AAV vector with the EF1 alpha promoter, and 137-fold higher expression than an AAV vector with the CMV promoter/enhancer. Although induction of the acute-phase response with the administration of lipopolysaccharide (LPS) activated the CMV promoter/enhancer from the context of an adenoviral vector in a previous study, LPS resulted in only a modest induction of this promoter from an AAV vector in vivo, An AAV vector with the CMV-beta -actin promoter upstream of the coagulation protein human factor X (hFX) was injected intravenously into neonatal mice. This resulted in expression of hFX at 548 ng/ml (6.8% of normal) for up to 1.2 years, and 0.6 copies of AAV vector per diploid genome in the liver at the time of sacrifice. Neonatal intramuscular injection resulted in expression of hFX at 248 ng/ml (3.1% of normal), which derived from both liver and muscle, We conclude that neonatal gene therapy with an AAV vector with the CMV-beta -actin promoter might correct hemophilia due to hFX deficiency.
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