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Shark Antibody Discovery Service
Sharks produce a unique heavy chain-only antibody called IgNAR (Immunoglobulin New Antigen Receptor). Its variable domain, VNAR (Variable New Antigen Receptor), is the smallest naturally occurring single-domain antibody, with a molecular weight of approximately 11–12 kDa. Unlike the VH/VL structure of conventional IgG antibodies, VNAR consists of only two complementarity-determining regions (CDRs): CDR1 and CDR3. Notably, CDR3 is longer and structurally more diverse than its counterpart in IgG, typically ranging from 15 to 17 amino acids.
Sequence analysis suggests that VNAR shares approximately 25–30% homology with the variable region of human antibodies. However, structural studies indicate a high degree of similarity between VNAR and human antibody variable regions, enabling potential humanization through framework transplantation.
Fig. 1 Schematic structure of different types of antibodies
Figure 2 Schematic diagram of different types of VNARs
(The left side shows the characterization of VNAR sequences, where black dots are typical cysteine residues, white dots are atypical amino acid residues, and black solid and dashed lines are disulfide bonds. On the right side are the 3D structural models of different types of VNARs, which were obtained by homology modeling of reported VNAR sequences with Pymol software)
Figure 3 Schematic structure of VH, VHH and VNAR
Key Features of VNAR
· Small and Compact – VNAR is the smallest known antigen-binding unit in nature (<11 kDa).
· Exceptional Stability – Exhibits high thermal stability and resistance to extreme pH conditions.
· High Affinity and Specificity – The extended CDR3 region enhances antigen recognition and binding.
· Versatile Engineering Potential – VNAR can be optimized through in vitro selection and artificial design, offering enhanced diversity and adaptability.
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