Ancient species offers contemporary therapeutics: an update on shark VNAR single domain antibody sequences, phage libraries and potential clinical applications
Open accessAbstract
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.
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Camelid VHH and shark V-NAR domains are used as templates to generate highly efficient and stable nanobodies.
“Given their high-affinity, solubility and stability also in absence of the partner VL domain, the camelid VH domains (VHH) [4] and the shark VH domains called V-NAR (New Antigen Receptor) [5], are currently used as templates to generate highly efficient and stable new antibody fragments collectively termed nanobodies [6,7,8].”
From Evolution of Escherichia coli Expression System in Producing Antibody Recombinant Fragments (2020) · cites this paper as [5]
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Ranibizumab and bevacizumab for neovascular age-related macular degeneration
(2011) · New England Journal of Medicine · doi:10.1056/nejmoa1102673 · Cited by 2,669 · see citing works
The structural analysis of shark IgNAR antibodies reveals evolutionary principles of immunoglobulins
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Evolution of Escherichia coli Expression System in Producing Antibody Recombinant Fragments
Sandomenico, A., Sivaccumar, J. P., & Ruvo, M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176324 · Cited by 134 · see citing works
- Authors
- English, H., Hong, J., & Ho, M.
- Affiliations
- National Cancer Institute (US)
- Corresponding author
- Ho, Mitchell
- Venue
- Antibody Therapeutics
- Publisher
- Oxford University Press (OUP)
- Published
- 2020-01
- Volume
- 3
- Issue
- 1
- Pages
- 1-9
- ISSN
- 2516-4236 (ISSN-L)
- PMC
- PMC7034638
- OpenAlex
- W3000763513
- Cited by
- 61
- References
- 2
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 10 · 2023: 12 · 2022: 12 · 2021: 5 · 2020: 6
- FWCI
- 1.29
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- public-domain
- Locations
- Antibody Therapeutics (publishedVersion, public-domain)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute
- NIH
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- nanobodies, phage display library, nurse shark, Ginglymostoma cirratum, cancer therapy
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