Shark IgNAR: The Next Broad Application Antibody in Clinical Diagnoses and Tumor Therapies?
Abstract
:1. Preface
2. Structural Characteristics and Advantages of IgNAR
2.1. Limitations of mAbs
2.2. Advantages of Shark-Derived VNAR
2.2.1. Structural Characteristics of Shark Monodomain Antibodies
2.2.2. Biochemical Characteristics of IgNAR
2.2.3. IgNAR Can Be Humanized
2.3. Preparation and Mass Production of Specific VNARs
2.3.1. Use of Chiloscyllium plagiosum as a Model Organism for VNAR Preparation
2.3.2. Phage Library Screening of Specific VNARs
2.3.3. Recombinant VNAR Production
3. Potential Applications of VNAR in Preclinical Test
3.1. Advantages in Drug Development and Clinical Treatment
3.2. Exploration and Development of VNAR-Based New Drugs
3.3. Application of VNAR as an Enzyme Inhibitor
3.4. VNARs Can Penetrate Tissues and Deliver Drugs across the Blood–Brain Barrier
4. Applications in Anti-Tumor Preclinical Studies
4.1. VNARs Have Stronger Affinity to Cancer-Specific Targeting Antigens
4.2. Strong and Rapid Tissue Permeability
4.3. The Next-Generation Antibody for Anti-Tumor Applications
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Conflicts of Interest
References
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V Region of mAbs | VHH | VNAR | ||
---|---|---|---|---|
Structural complexity | Complex post-translational modifications (glycoproteins) | +++ | — | — |
Expression in prokaryotic cells | — | +++ | +++ | |
Molecular weight | molecular weight (~kDa) | 50~75 | ~15 | ~12 |
Tissue penetration (BBB, ocular model, placental barrier) | — | ++ | +++ | |
Structural stability | Physiological and biochemical environment (high temperature, pH, urea) | — | +++ | +++ |
Shortcomings | Difficulty of humanization | — | + | +++ |
Drug | Application | Source | Clinical Trial Phase | Ref. |
---|---|---|---|---|
Caplacizumab | aTTP | VHH | 2019 FDA-approved | [76] |
AD214 | Idiopathic pulmonary fibrosis | VNAR | Phase I | [77] |
TXB4 | Primary central nervous system Lymphoma | VNAR | Preclinical | [78] |
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Jiang, X.; Sun, L.; Hu, C.; Zheng, F.; Lyu, Z.; Shao, J. Shark IgNAR: The Next Broad Application Antibody in Clinical Diagnoses and Tumor Therapies? Mar. Drugs 2023, 21, 496. https://doi.org/10.3390/md21090496
Jiang X, Sun L, Hu C, Zheng F, Lyu Z, Shao J. Shark IgNAR: The Next Broad Application Antibody in Clinical Diagnoses and Tumor Therapies? Marine Drugs. 2023; 21(9):496. https://doi.org/10.3390/md21090496
Chicago/Turabian StyleJiang, Xiaofeng, Ling Sun, Chengwu Hu, Feijian Zheng, Zhengbing Lyu, and Jianzhong Shao. 2023. "Shark IgNAR: The Next Broad Application Antibody in Clinical Diagnoses and Tumor Therapies?" Marine Drugs 21, no. 9: 496. https://doi.org/10.3390/md21090496