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胞内抗体(intracellular antibody,intrabody)是一类在细胞内表达、特异性地靶向胞内抗原以期实现对相应功能的调节甚至阻断的新型基因工程抗体。最常见的胞内抗体形式为单链抗体(ScFv)。通过相应定位信号肽序列,胞内抗体能定位于胞浆、胞核、内质网、线粒体、高尔基体、细胞膜和过氧化酶体等各种细胞器,以实现对靶标抗原的功能性调控。其应用也由早先的干扰病毒复制和抑制肿瘤生长,逐渐拓展至治疗中枢神经系统退行性疾病、自身免疫病以及抑制免疫排斥等方面。本文对胞内抗体的作用机制、筛选策略、优缺点、应用及跨膜抗体作一综述。
Intracellular antibodies (intracellular antibodies) are a group of novel genetically engineered antibodies that are expressed intracellularly and specifically target intracellular antigens to regulate or even block the function. The most common form of intracellular antibody is single-chain antibody (ScFv). Through the corresponding positioning of signal peptide sequences, intracellular antibodies can be localized in various organelles such as cytoplasm, nucleus, endoplasmic reticulum, mitochondria, Golgi apparatus, cell membrane and peroxisome to realize the functional regulation of target antigens. Its application is also from the earlier interference with virus replication and inhibition of tumor growth, and gradually extended to the treatment of central nervous system degenerative diseases, autoimmune diseases and inhibition of immune rejection and so on. In this paper, the mechanism of intracellular antibodies, screening strategies, advantages and disadvantages, applications and transmembrane antibodies are reviewed.