Mottershead D G, Alfthan K, Ojala K, Takkinen K, Oker-Blom C
Department of Biosciences, University of Helsinki, Helsinki, FIN-00014, Finland.
Biochem Biophys Res Commun. 2000 Aug 18;275(1):84-90. doi: 10.1006/bbrc.2000.3264.
Viral vectors displaying specific ligand binding moities such as scFv fragments or intact antibodies hold promise for the development of targeted gene therapy vectors. In this report we describe baculoviral vectors displaying either functional scFv fragments or the synthetic Z/ZZ IgG binding domain derived from protein A. Display on the baculovirus surface was achieved via fusion of the scFv fragment or Z/ZZ domain to the N-terminus of gp64, the major envelope protein of the Autographa californica nuclear polyhedrosis virus, AcNPV. As examples of scFv fragments we have used a murine scFv specific for the hapten 2-phenyloxazolone and a human scFv specific for carcinoembryonic antigen. In principle, the Z/ZZ IgG binding domain displaying baculoviruses could be targeted to specific cell types via the binding of an appropriate antibody. We envisage applications for scFv and Z/ZZ domain displaying baculoviral vectors in the gene therapy field.
展示特定配体结合部分(如单链抗体片段或完整抗体)的病毒载体有望用于开发靶向基因治疗载体。在本报告中,我们描述了展示功能性单链抗体片段或源自蛋白A的合成Z/ZZ IgG结合域的杆状病毒载体。通过将单链抗体片段或Z/ZZ结构域与苜蓿银纹夜蛾核型多角体病毒(AcNPV)的主要包膜蛋白gp64的N端融合,实现了在杆状病毒表面的展示。作为单链抗体片段的实例,我们使用了对半抗原2-苯基恶唑酮特异的鼠源单链抗体和对癌胚抗原特异的人源单链抗体。原则上,展示Z/ZZ IgG结合域的杆状病毒可通过合适抗体的结合靶向特定细胞类型。我们设想了展示单链抗体和Z/ZZ结构域的杆状病毒载体在基因治疗领域的应用。