The ACE2 Knockout 769-P Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population derived from the human 769-P clear cell renal carcinoma line. This product disrupts the ACE2 gene, creating a loss-of-function model for studies of ACE2-dependent biology. The polyclonal format provides a genetically heterogeneous mixture, ensuring robust target gene disruption while maintaining population-level reproducibility. It is intended for advanced biomedical research in renal epithelial contexts.
The parental 769-P line originates from human clear cell renal cell carcinoma and serves as a tumorigenic kidney epithelial model widely employed in renal cancer biology, drug response profiling, and host?Cpathogen interaction studies. These cells retain epithelial morphology, transport functions, and surface receptor expression??including TMPRSS2??making them suitable for investigating ACE2-dependent RAS modulation and SARS-CoV-2 entry in a kidney-derived context.
ACE2 operates as a carboxypeptidase that converts angiotensin II to angiotensin-(1-7), thereby counterbalancing the renin-angiotensin system (RAS). Its activity is modulated by upstream inputs such as angiotensin II, angiotensin I, ADAM17-mediated shedding, and interferon-alpha/gamma. ACE2 interacts with TMPRSS2 and B0AT1 (SLC6A19) at the cell surface. Downstream, angiotensin-(1-7) engages the MAS1 receptor, triggering signaling cascades involving AKT and nitric oxide synthase. Simultaneously, ACE2 acts as the primary receptor for SARS-CoV and SARS-CoV-2 spike proteins, facilitating viral entry in a TMPRSS2-dependent manner.
In the 769-P background, ACE2 knockout abolishes the conversion of angiotensin II to angiotensin-(1-7), eliminating a vital vasoprotective and anti-inflammatory arm of the RAS. This disruption shifts the balance toward angiotensin II/AT1R-driven vasoconstriction and pro-fibrotic signaling. Moreover, the knockout prevents SARS-CoV-2 entry by deleting the critical receptor, conferring cellular resistance to viral infection. This makes the model instrumental for dissecting how ACE2 loss influences RAS dysregulation, tumorigenic pathways, and antiviral responses in kidney epithelial cells.
Researchers can deploy these cells in SARS-CoV-2 pseudovirus entry assays, ACE2 enzymatic activity measurements, and angiotensin II/angiotensin-(1-7) quantification. Standard characterization via western blotting, RT-qPCR, immunofluorescence, and flow cytometry validates knockout and downstream signaling. The model further supports drug screening for ACE2-targeted therapies and SARS-CoV-2 entry inhibitors, as well as investigations into RAS?Crenal cell carcinoma crosstalk. For further information or product inquiries, please contact Ascent Research.
