Our catalog now includes two ACE2 Fc fusion proteins useful for coronavirus research. The Fc fusion proteins consist of the Fc domain of human IgG genetically linked to ACE2, the host cell receptor to which SARS-CoV-2 binds in order to initiate COVID-19 infection. The advantages of using ACE2 Fc fusion proteins lie mainly in their significantly increased half-life and stability compared to free ACE2 protein.
The ACE2 (angiotensin-converting enzyme 2) receptor is present in various areas throughout the body, including the blood vessels, intestines, nervous system, and most crucially for COVID-19 infection, lungs. Binding of coronavirus to ACE2 is mediated by the S1 subunit of the SARS-CoV-2 spike glycoprotein. (Our engineered recombinant antibodies against the spike glycoprotein are available here in various species, isotypes and subtypes.)
We now offer two types of ACE2 Fc fusion proteins, one with wild-type ACE2 (catalog # Pr00439) and one with the inactivated form of ACE2, ACE2-NN (catalog # Pr00441). Catalytically inactive ACE2-NN-Ig was generated from ACE2-Ig using H374N and H378N mutations in the ACE2 active site as described in a 2004 Journal of Virology paper.
Importantly, both Fc fusion proteins are offered as LALA mutants. LALA is a combination of L234A and L235A modifications, which together inactivate the Fc fragment by eliminating detectable binding to Fc receptors FcγRI, IIa and IIIa. Silencing the Fc effector function was performed to prevent potential antibody-dependent enhancement (ADE), a phenomenon observed where pathogen-specific antibodies or antibody fragments promote pathology.
Fc fusion proteins are valuable reagents for both in vivo and in vitro research. In vivo, the Fc domain dramatically prolongs the plasma half-life of the ACE2 protein. In vitro, the Fc fusion proteins can be used for common applications such as flow cytometry and protein binding assays. The Fc domain also improves in vivo and in vitro solubility and stability of ACE2. In addition, ACE2 Fc fusion proteins had been previously shown to potently inhibit SARS virus infection of cells, an effect that might be explained by the fact that ACE2 Fc fusion proteins were binding a considerable number of free virions and thus preventing their entry into the host cells.
The ELISA data below shows our ACE2 Fc fusion proteins binding to SARS-CoV-2. Our pricing and datasheets can be found here, while our other coronavirus-related reagents – which include the anti-SARS-CoV-2 antibody clone CR3022 and recombinant anti-human immunoglobulin antibodies – can be found here. Our next additions will include SARS-CoV-2 RBD Fc fusion proteins and anti-nucleocapsid protein antibodies.
Please contact us with any questions or to place an order.
Figure 1. ELISA: ACE2 Fc fusion protein binding to immobilized SARS-CoV-2 RBD Fc fusion protein. 96-well plate was coated with the SARS-CoV-2 RBD Fc fusion protein (Pr00444) at 5 ug/ml. The ACE2 Fc fusion protein (Pr00439) were titrated on a 3-fold serial dilution starting at 10 ug/ml.
Figure 2. RBD Fc binding to immobilized ACE2 Fc fusion proteins. 96-well plates were coated with the ACE2 Fc fusion proteins (Pr00439 and Pr00441) at 5 ug/ml. The SARS-CoV-2 RBD Fc fusion protein (Pr00444) conjugated to HRP was titrated on a 3-fold serial dilution starting at 10 ug/ml.
hubXchange | Antibody Therapeutics USA West
20th September 2022
San Fransisco, CA