Adeno-Associated Virus-Mediated Gene Transfer to Renal Tubule Cells via a Retrograde Ureteral Approach
Adeno-Associated Virus-Mediated Gene Transfer to Renal Tubule Cells via a Retrograde Ureteral Approach
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DOI：
10.1159/000333071
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发表时间：
2011-01-01
期刊：
影响因子：
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通讯作者：
Lipschutz, Joshua H.
中科院分区：
文献类型：
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作者：
Chung, Daniel C.;Ben Fogelgren;Lipschutz, Joshua H.
背景/目的：基因治疗涉及外源DNA的传递，以提供治疗蛋白。理想情况下，基因治疗载体应该是无毒的，非免疫原性的，容易生产的，有效地保护和传递DNA到靶细胞。方法：腺相关病毒（AAV）具有以上优点，缺点很少，目前已有100多株分离株。我们之前的研究表明，aav介导的基因疗法可以用于恢复Leber先天性黑朦患者的视力，这是一种儿童失明的疾病。结果：在体外细胞培养和小鼠体内实验中，新型重组蛋白AAV2/8和AAV2/9均能高效转导肾小管细胞。此外，我们调整和修改了逆行方法，以允许最佳的转基因递送到肾小管细胞，进一步减少免疫原性反应的风险。结论：我们相信重组AAV2，特别是AAV2/8，通过逆行途径将基因传递到肾小管细胞代表了一种可行的方法，用于基因治疗多种肾脏疾病，从常染色体显性多囊肾病到急性肾损伤。巴塞尔S. Karger股份有限公司版权所有
Background/Aims: Gene therapy involves delivery of exogenous DNA to provide a therapeutic protein. Ideally, a gene therapy vector should be non-toxic, non-immunogenic, easy to produce, and efficient in protecting and delivering DNA into target cells. Methods: Adeno-associated virus (AAV) offers these advantages and few, if any, disadvantages, and over 100 isolates exist. We previously showed that AAV-mediated gene therapy can be used to restore vision to patients with Leber's congenital amaurosis, a disease of childhood blindness. Results: Here we show that novel recombinant AAV2/8 and AAV2/9 transduce kidney tubule cells with high efficiency both in vitro in cell culture and in vivo in mice. In addition, we adapted and modified a retrograde approach to allow for optimal transgene delivery to renal tubular cells that further minimizes the risk of an immunogenic reaction. Conclusions: We believe that recombinant AAV2, especially AAV2/8, gene delivery to renal tubule cells via a retrograde approach represents a viable method for gene therapy for a multitude of renal disorders ranging from autosomal dominant polycystic kidney disease to acute kidney injury. Copyright (C) 2011 S. Karger AG, Basel