Study on molecular targeting using phage dispky library

本论文主要研究了利用噬菌体展示文库进行分子靶向治疗的方法，特别是对两种拟肽和三种人源单链抗体的特性进行了研究。1）肽拮抗剂和人源单链抗体的建立; 2）人源抗体的低分子形式的开发; 3）通过抗体工程开发新型生物功能分子。我们建立了可用于人类诊断和治疗方法的抗朊病毒scFv、抗淀粉样蛋白β scFv和抗IL-18抗体。关于2）：在抗淀粉样蛋白β的情况下，我们成功建立了具有淀粉样蛋白纤维化抑制活性的淀粉样蛋白β特异性VI片段。关于3）：我们试图研究在杂交瘤中使用AID（活化诱导的胞苷脱氨酶）活性使scFv亲和力成熟的方法。本研究采用腺病毒载体、逆转录病毒载体、常规脂质体DNA转染和脂质体转染等多种基因转染方法，检测了AID对杂交瘤细胞的转染效率

In this study, we studied about the molecular targeting using phage display library, particularly, on the characterization of two peptide mimics and three human scFv antibodies as candidates for human therapeutic reagents.1)Establishment of peptide antagonists and human antibodies for therapeutic purpose2)Development of low molecular forms of human antibodies3)Development of novel biofunctional molecules by antibody engineeringRegarding 1) : we established anti-prion scFv, anti-amyloid beta scFv and anti-IL-18 antibodies which are useful for human diagnostic and therapeutic approaches.Regarding 2) : In the case of anti-amyloid beta, we successfully established the amyloid beta-specific VI fragment with the inhibitory activity of amyloid fiblilization.Regarding 3) : we attempted to study the methodology for the affinity maturation of scFv using AID (activation-induced cytidine deaminase) activity in hybridomas. In this study, we examined the transfection efficiency of AID to hybridomas using various gene transfection methods such as adenovirus vector, retrovirus vector, usual electrophoretical DNA transfection or lipofectamine-transfection