In vivo transduction by intravenous injection of a lentiviral vector expressing human ADA into neonatal ADA gene knockout mice:: A novel form of enzyme replacement therapy for ADA deficiency
In vivo transduction by intravenous injection of a lentiviral vector expressing human ADA into neonatal ADA gene knockout mice:: A novel form of enzyme replacement therapy for ADA deficiency
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DOI：
10.1016/j.ymthe.2006.02.013
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发表时间：
2006-06-01
影响因子：
12.4
通讯作者：
Kohn, Donald B.
中科院分区：
文献类型：
--
作者：
Carbonaro, Denise A.;Jin, Xiangyang;Kohn, Donald B.
使用腺苷脱氨酶缺陷型严重联合免疫缺陷综合征（ADA 缺陷 SCID）小鼠模型，我们开发了一种非侵入性基因转移方法，用于人类 ADA 的持续全身表达，作为酶替代疗法。递送方法是基于人类免疫缺陷病毒1的慢病毒载体，在出生后第1天至第2天通过静脉注射全身给药。在本文中，我们描述了整合载体的生物分布、不同组织中 ADA 酶活性的表达水平，以及全身 ADA 表达在该小鼠模型中纠正 ADA 缺陷表型的功效。通过这种方法，主要通过肝脏和肺的转导实现了酶活性 ADA 的长期表达，恢复了免疫功能并显着延长了生存期。这些研究说明了体内持续产生酶活性 ADA 的潜力，作为频繁注射外源 ADA 蛋白治疗的替代方案。
Using a mouse model of adenosine deaminase-deficient severe combined immune deficiency syndrome (ADA-deficient SCID), we have developed a noninvasive method of gene transfer for the sustained systemic expression of human ADA as enzyme replacement therapy. The method of delivery is a human immunodeficiency virus 1-based lentiviral vector given systemically by intravenous injection on day I to 2 of life. In this article we characterize the biodistribution of the integrated vector, the expression levels of ADA enzyme activity in various tissues, as well as the efficacy of systemic ADA expression to correct the ADA-deficient phenotype in this mouse model. The long-term expression of enzymatically active ADA achieved by this method, primarily from transduction of liver and lung, restored immunologic function and significantly extended survival. These studies illustrate the potential for sustained in vivo production of enzymatically active ADA, as an alternative to therapy by frequent injection of exogenous ADA protein.