Zhang Lin-Hua, Song Cun-Xian, Wang Man-Yan, Yang Jing, Tang Li-Na
Tianjin Key Laboratory of Biomaterial Research, Laboratory of Drug Controlled Release, Institute of Biomedical Engineering, CAMS and PUMC, Tianjin 300192, China.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2006 Jun;28(3):350-4.
To study the feasibility of delivering viral gene vector from a collagen-coated polyurethane (PU) film through a mechanism involving monoclonal antiviral antibody tethering.
Anti-adenoviral monoclonal antibodies were covalently bound to the collagen-coated PU surface. These antibodies enabled tethering of replication defective adenoviruses through highly specific antigen-antibody affinity. The PU film-based gene delivery using antibody-tethered adenovirus encoding green fluorescent protein (GEP) was tested in rat arterial smooth muscle cell (A10 cell) culture in vitro. The virus binding stability was studied by incubating the collagen-coated PU film in PBS solution at 37 degrees C for 20 days, followed with A10 cell cultures with the incubated films and the corresponding buffer solution.
PU films with antibody-tethered adenovirus encoding GFP demonstrated efficient and highly localized gene delivery to A10 cells. Virus binding was stable for at least 10 days at physiological conditions, more than 77% of the originally bound virus remained in the film after 15 day's incubation.
Gene delivery using PU film-based anti-viral antibody tethering of vectors exhibited potentials of applications in a wide array of single or multiple therapeutic gene strategies, and in further stent-based gene delivery therapeutic strategies.
研究通过单克隆抗病毒抗体 tethering 机制从胶原包被的聚氨酯(PU)膜递送病毒基因载体的可行性。
将抗腺病毒单克隆抗体共价结合到胶原包被的 PU 表面。这些抗体通过高度特异性的抗原 - 抗体亲和力实现复制缺陷型腺病毒的 tethering。在体外大鼠动脉平滑肌细胞(A10 细胞)培养中测试使用抗体 tethered 编码绿色荧光蛋白(GEP)的腺病毒的基于 PU 膜的基因递送。通过将胶原包被的 PU 膜在 37℃的 PBS 溶液中孵育 20 天,然后用孵育过的膜和相应的缓冲溶液进行 A10 细胞培养来研究病毒结合稳定性。
带有抗体 tethered 编码 GFP 的腺病毒的 PU 膜向 A10 细胞展示了高效且高度局部化的基因递送。在生理条件下病毒结合至少稳定 10 天,孵育 15 天后超过 77%的最初结合的病毒仍保留在膜中。
使用基于 PU 膜的抗病毒抗体 tethering 载体进行基因递送在广泛的单基因或多基因治疗策略以及进一步基于支架的基因递送治疗策略中展现出应用潜力。