Structural insights and biomedical potential of IgNAR scaffolds from sharks

MAbs. 2015;7(1):15-25. doi: 10.4161/19420862.2015.989032.

Abstract

In addition to antibodies with the classical composition of heavy and light chains, the adaptive immune repertoire of sharks also includes a heavy-chain only isotype, where antigen binding is mediated exclusively by a small and highly stable domain, referred to as vNAR. In recent years, due to their high affinity and specificity combined with their small size, high physicochemical stability and low-cost of production, vNAR fragments have evolved as promising target-binding scaffolds that can be tailor-made for applications in medicine and biotechnology. This review highlights the structural features of vNAR molecules, addresses aspects of their generation using immunization or in vitro high throughput screening methods and provides examples of therapeutic, diagnostic and other biotechnological applications.

Keywords: CDR, complementarity-determining region; HV, hypervariable region; IgNAR; IgNAR V domain, variable domain of IgNAR; IgNAR, immunoglobulin new antigen receptor; VH, variable domain of the heavy chain; VHH, variable domain of camelid heavy chain antibodies; VL, variable domain of the light chain; antibody technology; biologic therapeutic; heavy chain antibody; mAbs, monoclonal antibodies; scFv, single chain variable fragment; shark; single chain binding domain; vNAR, variable domain of IgNAR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Fish Proteins / chemistry*
  • Fish Proteins / immunology
  • Immunoglobulin Heavy Chains / chemistry*
  • Immunoglobulin Heavy Chains / immunology
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Sharks

Substances

  • Fish Proteins
  • Immunoglobulin Heavy Chains