纳米抗体异源表达的研究进展

Heterologous Expression of Nanobodies: a Recent Progress

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。

Heavy chain antibodies（ HcAb） without light chains are naturally produced by camelids. The single domain antigen-binding fragment of Hc Ab is referred to as VHH or nanobody（ Nb）,which is the smallest antigen-binding entity at present. Several characteristics such as low molecular weight,high stability,and low immunogenicity make the use of nanobodies superior to the conventional antibodies. Currently,nanobodies are highly valuable antibodies for various applications, including fundamental research, diagnostics, and therapeutics. A variety of nanobodies are investigated in clinical researches. The recent progresses of heterologous expression of nanobodies in seven expression systems,including Gram-negative and positive bacteria,yeasts,filamentous fungi,insect cells,mammalian cells and plant cells were focused on,and the expression systems,hosts,characteristics of vectors,construction of vectors and yield of nanobodies were summarized. The strategies to increase the yield of nanobodies are discussed from molecular level,expression level and rational design.