Characterization of an Engineered Ace2 Protein for Its Improved Biological Features and Its Transduction Into Mscs: A Novel Approach to Combat Covid-19 Infection Publisher Pubmed



Hashemi ZS¹ ; Khalili S² ; Barough MS¹ ; Sarrami Forooshani R¹ ; Sanati H¹ ; Sarafrazi Esfandabadi F³ ; Rasaee MJ⁴ ; Nasirmoghadas P⁴
Source: International Journal of Biological Macromolecules Published:2024

Abstract

Transduced MSCs that express engineered ACE2 could be highly beneficial to combat COVID-19. Engineered ACE2 can act as decoy targets for the virus, preventing its entry into healthy lung cells. To this end, genetic engineering techniques were used to integrate the ACE2 gene into the MSCs genome. The MSCs were evaluated for proper expression and functionality. The mutated form of ACE2 was characterized using various techniques such as protein expression analysis, binding affinity against spike protein, thermal stability assessment, and enzymatic activity assays. The functionality of the mACE2 was assessed on SARS-CoV-2 using the virus-neutralizing test. The obtained results indicated that by introducing specific mutations in the ACE2 gene, the resulting mutant ACE2 had enhanced interaction with viral spike protein, its thermal stability was increased, and its enzymatic function was inhibited as a decoy receptor. Moreover, the mACE2 protein showed higher efficacy in the neutralization of the SARS-CoV-2. In conclusion, this study proposes a novel approach with potential benefits such as targeted drug delivery and reduced side effects on healthy tissues. These transduced MSCs can also be used in combination with other anti-COVID-19 treatments. Design of similar engineered biomolecules with desired properties could also be used to target other diseases. © 2024 Elsevier B.V.