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Review
. 2020 Jan;3(1):1-9.
doi: 10.1093/abt/tbaa001. Epub 2020 Jan 21.

Ancient species offers contemporary therapeutics: an update on shark VNAR single domain antibody sequences, phage libraries and potential clinical applications

Hejiao English  1   2 , Jessica Hong  1   2 , Mitchell Ho  1   2
Affiliations
Review

Ancient species offers contemporary therapeutics: an update on shark VNAR single domain antibody sequences, phage libraries and potential clinical applications

Hejiao English et al. Antib Ther. 2020 Jan.

Abstract

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 12-15 kDa. 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 naïve 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.

Keywords: VNAR single domain; antibody engineering; next-generation sequencing; nurse shark (Ginglymostoma cirratum); phage display library.

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Figures

Figure 1
Figure 1
Schematic depiction of human IgG, shark IgNAR and VNAR structures.
Figure 2
Figure 2
Shark VNAR Types I-IV based on the recent NGS analysis of 1.2 million adult nurse shark VNAR sequences. The two canonical cysteines (21C and 82C) are in white circles, whereas the extra cysteines are in black circles. The variable regions are marked as CDR1, HV2, HV4 and CDR3. All the disulfide bridges are shown using connected black lines. Type I (21C, 34C and 82C) and Type II (21C, 28C and 82C) VNARs contain three canonical cysteines as indicated. Subtypes in Type I and Type II VNARs contain 3–9 cysteines.
See this image and copyright information in PMC

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