Iranian Journal of Diabetes and Obesity
Shahid Sadoughi University Of Medical Sciences
Sun, Jun 30, 2024
[Archive]
Volume 16, Issue 2 (volume 16, number 2 2024)
IJDO 2024, 16(2): 112-121 |
Back to browse issues page
Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Sefid F, Monshizadeh K, Azamirad G, Vahidi Mehrjardi M Y. Antibody Engineering to Enhancement of Ranibizumab Binding Affinity for the Prevention and Treatment of Diabetic Retinopathy. IJDO 2024; 16 (2) :112-121
URL: http://ijdo.ssu.ac.ir/article-1-875-en.html
URL: http://ijdo.ssu.ac.ir/article-1-875-en.html
Diabetes Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
Abstract: (61 Views)
Objective: The VEGF function blockage effectively reduces the progression of diabetic retinopathy. Ranibizumab and bevacizumab are some anti-VEGF monoclonal antibodies (mAb). Considering the importance of affinity maturation of ranibizumab, we aimed to find the essential amino acids of the ranibizumab antibody (Ab).
Materials and Methods: We tried to find the important amino acids of this antibody via Paratome, Meta-PPISP, and the WESA web server. Subsequently, these amino acids were mutated to improve the binding affinity of the Ab variants to antigen (Ag). In this regard, the ranibizumab anti-VEGF-A was mutated. The structural docking prediction of the ranibizumab-VEGF-A complex was used for the design and validation of ranibizumab with a higher affinity for binding to VEGF-A. Finally, we measured the binding affinity of Ab variants to Ag by computational docking.
Results: Bioinformatic analyzes such as molecular docking and dynamics showed that several mutant variants successfully improved the properties of Ab binding compared to the wild-type Ab.
Conclusion: Consistent with the use of anti-VEGF monoclonal antibodies in the treatment of diabetic retinopathy, the mutant variants of ranibizumab may be potential candidates for stronger affinity binding to VEGF, which may affect the specificity and sensitivity of the antibody.
Materials and Methods: We tried to find the important amino acids of this antibody via Paratome, Meta-PPISP, and the WESA web server. Subsequently, these amino acids were mutated to improve the binding affinity of the Ab variants to antigen (Ag). In this regard, the ranibizumab anti-VEGF-A was mutated. The structural docking prediction of the ranibizumab-VEGF-A complex was used for the design and validation of ranibizumab with a higher affinity for binding to VEGF-A. Finally, we measured the binding affinity of Ab variants to Ag by computational docking.
Results: Bioinformatic analyzes such as molecular docking and dynamics showed that several mutant variants successfully improved the properties of Ab binding compared to the wild-type Ab.
Conclusion: Consistent with the use of anti-VEGF monoclonal antibodies in the treatment of diabetic retinopathy, the mutant variants of ranibizumab may be potential candidates for stronger affinity binding to VEGF, which may affect the specificity and sensitivity of the antibody.
Type of Study: Research |
Subject:
Special
Received: 2024/03/11 | Accepted: 2024/05/2 | Published: 2024/06/21
Received: 2024/03/11 | Accepted: 2024/05/2 | Published: 2024/06/21
References
1. Dehghani M, Zarch SM, Mehrjardi MY, Nazari M, Babakhanzadeh E, Ghadimi H, et al. Evaluation of miR-181b and miR-126-5p expression levels in T2DM patients compared to healthy individuals: relationship with NF-κB gene expression. Endocrinologia, diabetes y nutricion. 2020;67(7):454-60. [DOI:10.1016/j.endinu.2019.09.009]
2. Rahvarzadeh Z, Dehghanian M, Mehrjardi MY, Ashkezari MD. Investigating the Relation between LCK Gene Expression with Type 2 Diabetes Patients in Yazd Diabetes Research Center. Iranian journal of diabetes and obesity. 2022;14(1): 14-19. [DOI:10.18502/ijdo.v14i1.8736]
3. Sefid F, Azamirad G, Asadollahi S, Kalantar SM, Khalilzade SH, Mehrjardi MY. Common Polymorphisms Identified In Patients with Type 2 Diabetes Mellitus Revealed From Next-Generation Sequencing Analysis. Iranian journal of diabetes and obesity.2023;15(2):73-80. [DOI:10.18502/ijdo.v15i2.12964]
4. Luqman F, Bibi H, Mukhtar M, Zafar F, Ahmed H, Khizer MA, et al. Transient Intraocular Pressure Fluctuations After Intravitreal Bevacizumab Injection in Proliferative Diabetic Retinopathy Patients: A Prospective Study. Cureus. 2023;15(9):e45371. [DOI:10.7759/cureus.45371]
5. Behl T, Kotwani A. Exploring the various aspects of the pathological role of vascular endothelial growth factor (VEGF) in diabetic retinopathy. Pharmacological research. 2015;99:137-48. [DOI:10.1016/j.phrs.2015.05.013]
6. Zhao Y, Singh RP. The role of anti-vascular endothelial growth factor (anti-VEGF) in the management of proliferative diabetic retinopathy. Drugs in context. 2018;7:212532. [DOI:10.7573/dic.212532]
7. Bolinger MT, Antonetti DA. Moving past anti-VEGF: novel therapies for treating diabetic retinopathy. International journal of molecular sciences. 2016;17(9):1498. [DOI:10.3390/ijms17091498]
8. Osaadon P, Fagan XJ, Lifshitz T, Levy J. A review of anti-VEGF agents for proliferative diabetic retinopathy. Eye. 2014;28(5):510-20. [DOI:10.1038/eye.2014.13]
9. Bahr TA, Bakri SJ. Update on the management of diabetic retinopathy: Anti-VEGF agents for the prevention of complications and progression of nonproliferative and proliferative retinopathy. Life. 2023;13(5):1098. [DOI:10.3390/life13051098]
10. Stewart MW. A review of ranibizumab for the treatment of diabetic retinopathy. Ophthalmology and therapy. 2017; 6(1):33-47. [DOI:10.1007/s40123-017-0083-9]
11. Buratto D, Wan Y, Shi X, Yang G, Zonta F. In silico maturation of a nanomolar antibody against the human CXCR2. Biomolecules. 2022;12(9):1285. [DOI:10.3390/biom12091285]
12. Ko BK, Choi S, Cui LG, Lee YH, Hwang IS, Kim KT, et al. Affinity maturation of monoclonal antibody 1E11 by targeted randomization in CDR3 regions optimizes therapeutic antibody targeting of HER2-positive gastric cancer. PloS one. 2015;10(7):e0134600. [DOI:10.1371/journal.pone.0134600]
13. Payandeh Z, Rajabibazl M, Mortazavi Y, Rahimpour A, Taromchi AH, Dastmalchi S. Affinity maturation and characterization of the ofatumumab monoclonal antibody. Journal of cellular biochemistry. 2019;120(1):940-50. [DOI:10.1002/jcb.27457]
14. Barderas R, Desmet J, Timmerman P, Meloen R, Casal JI. Affinity maturation of antibodies assisted by in silico modeling. Proceedings of the National Academy of Sciences. 2008;105(26):9029-34. [DOI:10.1073/pnas.0801221105]
15. Lim CC, Choong YS, Lim TS. High Affinity Maturated Human Antibodies from Naïve and Synthetic Antibody Repertoires.Antibody Engineering. 2018. [DOI:10.5772/intechopen.71664]
16. Barderas R, Desmet J, Alard P, Casal JI. Affinity maturation by semi-rational approaches. Antibody Engineering: Methods and Protocols, Second Edition. 2012 ;907:463-86. [DOI:10.1007/978-1-61779-974-7_27]
17. Muyldermans S. A guide to: generation and design of nanobodies. The FEBS journal. 2021;288(7):2084-102. [DOI:10.1111/febs.15515]
18. Gross JG, Glassman AR. A novel treatment for proliferative diabetic retinopathy: anti-vascular endothelial growth factor therapy. JAMA ophthalmology. 2016;134(1):13-4. [DOI:10.1001/jamaophthalmol.2015.5079]
19. Jiang Y, Leiderman YI. Treatment Strategy in Proliferative Diabetic Retinopathy: Anti-VEGF, Laser, or Both?. Journal of VitreoRetinal Diseases. 2018;2(5):302-4. [DOI:10.1177/2474126418785308]
20. Singh RP, Elman MJ, Singh SK, Fung AE, Stoilov I. Advances in the treatment of diabetic retinopathy. Journal of Diabetes and its Complications. 2019;33(12):107417. [DOI:10.1016/j.jdiacomp.2019.107417]
21. Shehata L, Maurer DP, Wec AZ, Lilov A, Champney E, Sun T, et al. Affinity maturation enhances antibody specificity but compromises conformational stability. Cell reports. 2019;28(13):3300-8. [DOI:10.1016/j.celrep.2019.08.056]
22. Bessalah S, Jebahi S, Mejri N, Salhi I, Khorchani T, Hammadi M. Perspective on therapeutic and diagnostic potential of camel nanobodies for coronavirus disease-19 (COVID-19). 3 Biotech. 2021;11(2):89. [DOI:10.1007/s13205-021-02647-5]
23. Nardi GM, Ferrara E, Converti I, Cesarano F, Scacco S, Grassi R, et al. Does diabetes induce the vascular endothelial growth factor (VEGF) expression in periodontal tissues? A systematic review. International journal of environmental research and public health. 2020;17(8):2765. [DOI:10.3390/ijerph17082765]
24. Gahoual R, François YN, Mignet N, Houzé P. Emerging biotechnological approaches with respect to tissue regeneration: from improving biomaterial incorporation to comprehensive omics monitoring. InBiomaterials for Organ and Tissue Regeneration.Woodhead Publishing.2020 :83-112. [DOI:10.1016/B978-0-08-102906-0.00017-9]
| Rights and permissions | |
 |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
