Ancient species offers contemporary therapeutics: an update on shark VNAR single domain antibody sequences, phage libraries and potential clinical applications.
Ancient species offers contemporary therapeutics: an update on shark VNAR single domain antibody sequences, phage libraries and potential clinical applications.
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DOI：
10.1093/abt/tbaa001
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发表时间：
2020-01-01
影响因子：
--
通讯作者：
Ho, Mitchell
中科院分区：
文献类型：
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作者：
English, Hejiao;Hong, Jessica;Ho, Mitchell
鲨鱼免疫球蛋白新抗原受体（IgNAR）的抗原结合可变区（VNAR）在大约5亿年前进化而来，是动物界中最小的抗体片段之一，大小为12- 15 kDa。本文综述了鲨鱼VNAR单结构域序列的现有知识和鲨鱼VNAR作为研究工具和潜在治疗方法的持续发展，特别强调了最近对120万条鲨鱼VNAR序列的下一代测序分析和从6条幼稚成年护士鲨（Ginglymostoma cirratum）构建大型噬菌体展示鲨鱼VNAR文库。大型噬菌体展示的VNAR单域库涵盖了所有四种已知的VNAR类型（类型I-IV）和许多以前未知的类型。正在进行的临床前开发将有助于确定鲨鱼VNAR单域作为治疗癌症和其他人类疾病的潜在新候选药物家族的效用。
The antigen binding variable domain (VNAR) of the shark immunoglobulin new antigen receptor (IgNAR) evolved approximately 500 million years ago and it is one of the smallest antibody fragments in the animal kingdom with sizes of 12-15kDa. This review discusses the current knowledge of the shark VNAR single domain sequences and ongoing development of shark VNARs as research tools as well as potential therapeutics, in particular highlighting the recent next-generation sequencing analysis of 1.2 million shark VNAR sequences and construction of a large phage displayed shark VNAR library from six naive adult nurse sharks (Ginglymostoma cirratum). The large phage-displayed VNAR single domain library covers all the four known VNAR types (Types I-IV) and many previously unknown types. Ongoing preclinical development will help define the utility of shark VNAR single domains as a potentially new family of drug candidates for treating cancer and other human diseases.