Increased hepatic transduction with reduced systemic dissemination and proinflammatory cytokines following hydrodynamic injection of helper-dependent adenoviral vectors

被引:58
作者
Brunetti-Pierri, N
Palmer, DJ
Mane, V
Finegold, M
Beaudet, AL
Ng, P
机构
[1] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA
[2] Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA
关键词
helper-dependent adenoviral vectors; gutless; adenovirus; hydrodynamic; gene therapy; liver; hepatocytes; kupffer cells; cytokines;
D O I
10.1016/j.ymthe.2005.03.001
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Hydrodynamic injection of helper-dependent adenoviral vectors (HDAd) in mice results in increased hepatic transduction, reduced splenic and pulmonary transduction, and reduced levels of the proinflammatory cytokines IL-6 and IL-12 compared to conventional injection. These results indicate that hepatic transduction by HDAd, at least alone, does not necessarily provoke a severe innate inflammatory response. Instead, they suggest that systemic vector dissemination may play a major role in the severity of the innate inflammatory response. These results further suggest that the safety and efficacy of HDAd-mediated, liver-directed gene therapy may be improved if the vector could be preferentially, if not exclusively, targeted to liver.
引用
收藏
页码:99 / 106
页数:8
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