Shark VNAR phage display libraries: An alternative source for therapeutic and diagnostic recombinant antibody fragments

• Published in: Fish & shellfish immunology Vol. 138; p. 108808
• Main Authors: Manoutcharian, Karen, Gevorkian, Goar
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-07-2023
• Subjects: Affinity maturation; Nanobody; Phage display library; Recombinant antibody fragments; Shark variable new antigen receptor (VNARs); Phage display library; Nanobody; Affinity maturation; Shark variable new antigen receptor (VNARs); Recombinant antibody fragments
• ISSN: 1050-4648; 1095-9947
• DOI: 10.1016/j.fsi.2023.108808

The development of recombinant antibody fragments as promising alternatives to full-length immunoglobulins offers vast opportunities for biomedicine. Antibody fragments have important advantages compared with conventional monoclonal antibodies that make them attractive for the biotech industry: superior stability and solubility, reduced immunogenicity, higher specificity and affinity, capacity to target the hidden epitope and cross the blood-brain barrier, the ability to refold after heat denaturation and inexpensive and easy large-scale production. Different antibody formats such as antigen-binding fragments (Fab), single-chain fragment variable (scFv) consisting of the antigen-binding domains of Ig heavy (VH) and light (VL) chain regions connected by a flexible peptide linker, single-domain antibody fragments (sdAbs) like camelid heavy-chain variable domains (VHHs) and shark variable new antigen receptor (VNARs), and bispecific antibodies (bsAbs) are currently being evaluated as diagnostics or therapeutics in preclinical studies and clinical trials. In the present review, we summarize and discuss studies on VNARs, the smallest recombinant antibody fragment, obtained after the screening of different types of phage display antibody libraries. Results published until March 2023 are discussed.
•Antibody fragments are promising alternatives to full-length immunoglobulins.•Different antibody formats are currently being studied in pre-clinical models.•Shark variable new antigen receptor (VNAR) antibodies have unique characteristics.•Shark VNAR antibodies are attractive molecules for the biotech industry.