Antibody Engineering to Enhancement of Ranibizumab Binding Affinity for the Prevention and Treatment of Diabetic Retinopathy

Fateme Sefid; Kimia Monshizadeh; Ghasem Azamirad; Mohammad Yahya  Vahidi Mehrjardi

doi:10.18502/ijdo.v16i2.15710

Fateme Sefid Department of Medical Genetics, Shahid Sadoughi University of Medical Science, Yazd, Iran Department of Medical Genetics, Shahid Sadoughi University of Medical Science, Yazd, Iran
Kimia Monshizadeh Department of Medical Genetics, Shahid Sadoughi University of Medical Science, Yazd, Iran
Ghasem Azamirad Department of Mechanical Engineering, Yazd University, Yazd, Iran
Mohammad Yahya Vahidi Mehrjardi Diabetes Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

DOI: https://doi.org/10.18502/ijdo.v16i2.15710

Keywords: Antibody engineering, Anti-VEGF-A, Bioinformatic, Binding affinity, Ranibizumab

Abstract

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.