Targeting of Adenovirus Serotype 5 (Ad5) and 5/47 Pseudotyped Vectors In Vivo: Fundamental Involvement of Coagulation Factors and Redundancy of CAR Binding by Ad5
Targeting of Adenovirus Serotype 5 (Ad5) and 5/47 Pseudotyped Vectors In Vivo: Fundamental Involvement of Coagulation Factors and Redundancy of CAR Binding by Ad5
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DOI：
10.1128/jvi.00663-07
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发表时间：
2007-06
影响因子：
5.4
通讯作者：
S. Waddington;A. Parker;M. Havenga;S. Nicklin;S. Buckley;J. McVey;A. Baker
中科院分区：
文献类型：
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作者：
S. Waddington;A. Parker;M. Havenga;S. Nicklin;S. Buckley;J. McVey;A. Baker
维生素K依赖性凝血因子在体外可促进腺病毒细胞转导。在体内，华法林预处理消除了CAR结合能力缺失的腺病毒血清型5（Ad 5）载体的肝靶向。在这里，我们评估在体内转导和生物分布的Ad 5载体与未修饰的纤维（Ad 5）和血清型47纤维假型Ad 5（Ad 5/47;亚组D）病毒血管内注射后。Warcanty减少了两种病毒的肝脏转导。然而，未观察到对早期肝病毒蓄积的影响，表明对枯否细胞相互作用无影响。因此，凝血因子在选择性介导Ad 5和Ad 5/47载体的肝细胞转导中起关键作用。
ABSTRACT Vitamin K-dependent coagulation factors can promote adenoviral cell transduction in vitro. In vivo, warfarin pretreatment ablates liver targeting of an adenovirus serotype 5 (Ad5) vector deleted of CAR binding capability. Here, we assess in vivo transduction and biodistribution of Ad5 vectors with nonmodified fibers (Ad5) and a serotype 47 fiber-pseudotyped Ad5 (Ad5/47; subgroup D) virus following intravascular injection. Warfarin reduced liver transduction by both viruses. However, no impact on early liver virus accumulation was observed, suggesting no effect on Kupffer cell interactions. Hence, coagulation factors play a pivotal role in selectively mediating liver hepatocyte transduction of Ad5 and Ad5/47 vectors.