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羊驼体内存在天然缺失轻链的重链抗体(HcAb),其单域抗原结合片段也称为VHH或纳米抗体(nanobody,Nb),是目前已知的最小抗原结合片段。与传统抗体相比,纳米抗体具有分子量小(12~15kDa)、稳定性好和免疫原性低等特点,这些特点使得VHH在基础研究、诊断及治疗上具有极大的应用价值,目前已有多种纳米抗体进入了临床研究阶段。综述了近年来VHH在革兰氏阴性菌(大肠杆菌)、革兰氏阳性菌(芽孢杆菌和乳酸杆菌)、酵母、丝状真菌、昆虫细胞、哺乳动物细胞和植物细胞中异源表达的研究现状,包括表达系统、宿主、载体特点、载体构建方式及产量等;从分子水平、表达水平和理性设计三个层面探讨了纳米抗体产量提高的策略,以期为纳米抗体研究者提供借鉴和思路。
The alpaca body contains a heavy chain antibody (HcAb) with a natural deletion of the light chain, and its single domain antigen-binding fragment, also called VHH or nanobody (Nb), is the smallest antigen-binding fragment known so far. Compared with traditional antibodies, Nanobodies have the characteristics of small molecular weight (12 ~ 15kDa), good stability and low immunogenicity, which make VHH have great application value in basic research, diagnosis and treatment. At present, A variety of nano-antibodies entered the clinical research stage. The recent studies on the heterologous expression of VHH in Gram-negative bacteria (Escherichia coli), Gram-positive bacteria (Bacillus and Lactobacillus), yeasts, filamentous fungi, insect cells, mammalian cells and plant cells The current situation, including expression system, host, vector characteristics, vector construction methods, yield and so on, were discussed in terms of molecular level, expression level and rational design in order to provide reference and ideas for the researchers of Nanobody.