Marschall Andrea L J, Dübel Stefan
Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Institute of Biochemistry, Biotechnology and Bioinformatics, Technische Universität Braunschweig, Spielmannstr.7, 38106 Braunschweig, Germany.
Comput Struct Biotechnol J. 2016 Jul 31;14:304-8. doi: 10.1016/j.csbj.2016.07.003. eCollection 2016.
Challenges posed by complex diseases such as cancer, chronic viral infections, neurodegenerative disorders and many others have forced researchers to think beyond classic small molecule drugs, exploring new therapeutic strategies such as therapy with RNAi, CRISPR/Cas9 or antibody therapies as single or as combination therapies with existing drugs. While classic antibody therapies based on parenteral application can only reach extracellular targets, intracellular application of antibodies could provide specific advantages but is so far little recognized in translational research. Intrabodies allow high specificity and targeting of splice variants or post translational modifications. At the same time off target effects can be minimized by thorough biochemical characterization. Knockdown of cellular proteins by intrabodies has been reported for a significant number of disease-relevant targets, including ErbB-2, EGFR, VEGFR-2, Metalloproteinase MMP2 and MMP9, β-amyloid protein, α-synuclein, HIV gp120, HCV core and many others. This review outlines the recent advances in ER intrabody technology and their potential use in therapy.
癌症、慢性病毒感染、神经退行性疾病等复杂疾病带来的挑战迫使研究人员超越传统小分子药物进行思考，探索新的治疗策略，如RNA干扰疗法、CRISPR/Cas9疗法或抗体疗法，作为单一疗法或与现有药物的联合疗法。虽然基于肠胃外给药的传统抗体疗法只能作用于细胞外靶点，但抗体的细胞内应用可能具有特定优势，但目前在转化研究中尚未得到充分认可。胞内抗体具有高特异性，能够靶向剪接变体或翻译后修饰。同时，通过全面的生化特性分析可以将脱靶效应降至最低。据报道，针对大量与疾病相关的靶点，包括ErbB-2、表皮生长因子受体（EGFR）、血管内皮生长因子受体-2（VEGFR-2）、金属蛋白酶MMP2和MMP9、β-淀粉样蛋白、α-突触核蛋白、HIV gp120、丙肝病毒核心蛋白等，胞内抗体可实现细胞内蛋白质的敲低。本文综述了内质网胞内抗体技术的最新进展及其在治疗中的潜在应用。
