Immobilization of gene vectors on polyurethane surfaces using a monoclonal antibody for localized gene delivery
Immobilization of gene vectors on polyurethane surfaces using a monoclonal antibody for localized gene delivery
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DOI：
10.1002/jgm.912
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发表时间：
2006-06-01
影响因子：
3.5
通讯作者：
Levy, R. J.
中科院分区：
文献类型：
--
作者：
Mei, Lin;Jin, Xu;Levy, R. J.
传统的利用病毒载体进行基因治疗的策略导致了病毒载体的次优定位和潜在的危险远端传播。我们假设腺病毒基因载体可以通过一种涉及抗病毒抗体栓系的机制，在聚氨酯（PU）薄膜上实现局部递送。方法采用胶原包衣制备聚氨酯薄膜。抗腺病毒单克隆抗体与胶原表面共价结合。这些抗体通过高度特异性的抗原-抗体亲和力使复制缺陷腺病毒[Ad-GFP（编码绿色荧光蛋白）]得以捆绑。研究了病毒在PU膜上的结合稳定性和体外传递。大鼠动脉平滑肌细胞（A10）的细胞培养研究评估了PU基质上或附近的转导。胶原包被PU膜的体内实验研究了约克郡猪心房心外膜和皮下植入模型。结果我们首次报道了利用编码绿色荧光蛋白（GFP）的抗体拴系腺病毒在PU膜上成功地将基因传递到细胞培养和猪移植的动脉平滑肌细胞，显示出高效和高度定位的基因传递。相比之下，将病毒载体直接注射到皮下部位会产生稀疏的、针状轨迹导向的GFP表达模式。结论PU膜是一种适合于可定位的病毒载体传递系统的平台，可以防止病毒载体的全身传播。使用基于PU膜的抗病毒抗体系缚载体的基因传递应该适用于广泛的单一或多种治疗基因策略，以及进一步的基于设备的基因传递治疗策略。版权所有(c) 2006约翰威利父子有限公司
Background Conventional strategies of gene therapy using viral vectors result in suboptimal localization and potentially dangerous distal spread of vector. We hypothesized that localized delivery of adenoviral gene vectors could be achieved from a polyurethane (PU) film through a mechanism involving anti-viral antibody tethering.Methods PU films were formulated with a collagen coating. Anti-adenoviral monoclonal antibodies were covalently bound to the collagen surface. These antibodies enabled tethering of replication-defective adenoviruses [Ad-GFP (encoding green fluorescent protein)] through highly specific antigen-antibody affinity. The binding stability and in vitro delivery of virus bound on PU films were investigated. Cell culture studies with rat arterial smooth muscle cells (A10) assessed transduction on or near the PU matrix. In vivo experiments with collagen-coated PU films investigated atrial epicardial implant and subdermal implant models in Yorkshire swine.Results We report for the first time successful PU film-based gene delivery using antibody-tethered adenovirus encoding the green fluorescent protein (GFP), demonstrating efficient and highly localized gene delivery to arterial smooth muscle cells in cell culture and pig implant. In comparison, direct injections of viral vectors into subcutaneous sites gave sparse, needle-track-oriented GFP expression patterns.Conclusion We conclude that PU film is a suitable platform for a localizable viral vector delivery system that also prevents systemic spread of vector. Gene delivery using PU film-based anti-viral antibody tethering of vectors should be suitable for a wide array of single or multiple therapeutic gene strategies, and for further device-based gene delivery therapeutic strategies. Copyright (c) 2006 John Wiley & Sons, Ltd.