2. Academic Validation
  3. Characterization and humanization of VNARs targeting human serum albumin from the whitespotted bamboo shark (Chiloscyllium plagiosum)

Characterization and humanization of VNARs targeting human serum albumin from the whitespotted bamboo shark (Chiloscyllium plagiosum)

  • Int J Biol Macromol. 2024 Jun 13;273(Pt 2):133082. doi: 10.1016/j.ijbiomac.2024.133082.
Weijie Li 1,  Mingliang Chen 2,  Tao Wang 3,  Xin Feng 4,  Xierui Jiang 1,  Xiaoning Dong 5,  Huan Zhang 1,  Xixiang Tang 6,  Rui Tian 7,  Yongyou Zhang 8,  Zengpeng Li 9
Affiliations

Affiliations

  • 1 State Key Laboratory Breeding Base of Marine Genetic Resources, Third Institute of Oceanography, Ministry of Natural Resources, Xiamen, Fujian 361005, China.
  • 2 State Key Laboratory Breeding Base of Marine Genetic Resources, Third Institute of Oceanography, Ministry of Natural Resources, Xiamen, Fujian 361005, China; School of Marine Biology, Xiamen Ocean Vocational College, Xiamen, Fujian 361100, China. Electronic address: mlchen_gg@tio.org.cn.
  • 3 The Key Laboratory of Urinary Tract Tumors and Calculi, Department of Urology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, 361003, China.
  • 4 State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Xiamen University, Xiamen, Fujian 361102, China.
  • 5 State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, Engineering Research Centre of Molecular Diagnostics of the Ministry of Education, National Institute for Data Science in Health and Medicine Engineering, Faculty of Medicine and Life Sciences, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China; School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian 361102, China.
  • 6 State Key Laboratory Breeding Base of Marine Genetic Resources, Third Institute of Oceanography, Ministry of Natural Resources, Xiamen, Fujian 361005, China. Electronic address: tangxixiang@tio.org.cn.
  • 7 State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Xiamen University, Xiamen, Fujian 361102, China. Electronic address: rtian@xmu.edu.cn.
  • 8 State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, Engineering Research Centre of Molecular Diagnostics of the Ministry of Education, National Institute for Data Science in Health and Medicine Engineering, Faculty of Medicine and Life Sciences, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China. Electronic address: yongyouzhang@xmu.edu.cn.
  • 9 State Key Laboratory Breeding Base of Marine Genetic Resources, Third Institute of Oceanography, Ministry of Natural Resources, Xiamen, Fujian 361005, China. Electronic address: lizengpeng@tio.org.cn.
PMID: 38878923 DOI: 10.1016/j.ijbiomac.2024.133082
Abstract

The Shark-derived immunoglobulin new antigen receptors (IgNARs) have gained increasing attention for their high solubility, exceptional thermal stability, and intricate sequence variation. In this study, we immunized whitespotted bamboo shark (Chiloscyllium plagiosum) to create phage display library of variable domains of IgNAR (VNARs) for screening against Human Serum Albumin (HSA), a versatile vehicle in circulation due to its long in vivo half-life. We identified two HSA-binding VNAR clones, 2G5 and 2G6, and enhanced their expression in E. coli with the FKPA chaperone. 2G6 exhibited a strong binding affinity of 13 nM with HSA and an EC50 of 1 nM. In vivo study with a murine model further provided initial validation of 2G6's ability to prolong circulation time by binding to HSA. Additionally, we employed computational molecular docking to predict the binding affinities of both 2G6 and its humanized derivative, H2G6, to HSA. Our analysis unveiled that the complementarity-determining regions (CDR1 and CDR3) are pivotal in the antigen recognition process. Therefore, our study has advanced the understanding of the potential applications of VNARs in biomedical research aimed at extending drug half-life, holding promise for future therapeutic and diagnostic progressions.

Keywords

HSA; VNAR; Whitespotted bamboo shark.

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