The CD46 Knockout 786-O Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the 786-O human epithelial cell line. This product features a targeted disruption of the CD46 gene, eliminating expression of the membrane cofactor protein and creating a loss-of-function model for complement regulation, viral pathogenesis, and immune modulation studies. The polyclonal nature of the knockout population ensures a heterogeneous genetic background, capturing diverse functional responses without selection for a single clonal isolate. This cell model is optimized for researchers investigating CD46-dependent mechanisms in renal cell carcinoma and related biological pathways.
The parental 786-O cell line originates from a primary clear cell renal cell carcinoma and is widely employed as a model for ccRCC, the most common form of kidney cancer. These epithelial cells harbor a well-characterized von Hippel-Lindau (VHL) tumor suppressor gene mutation, rendering them tumorigenic and reflective of the dysregulated hypoxia response and metabolic reprogramming observed in ccRCC. The 786-O background provides a clinically relevant system to dissect how CD46 contributes to tumor cell interactions with the complement system and adaptive immunity within the renal carcinoma microenvironment.
CD46 functions as a ubiquitously expressed type I transmembrane glycoprotein that protects cells from autologous complement attack. It acts as a cofactor for the serine protease factor I, which cleaves deposited C3b and C4b into inactive fragments, preventing formation of the C3 convertase and subsequent membrane attack complex assembly. Beyond complement regulation, CD46 mediates cellular entry for measles virus hemagglutinin and adenovirus fiber, participates in sperm-egg fusion, and modulates adaptive immunity. Its expression is modulated by upstream signals including complement C3b/C4b opsonins, TNF-alpha, and IL-1beta, and it drives downstream events such as IL-10 production and CD4+ T-cell differentiation. Knockout of CD46 therefore disrupts a network involving complement factor I, viral adhesion proteins, and immunoregulatory circuits.
In the 786-O ccRCC context, CD46 knockout is particularly valuable for exploring how tumor cells evade complement-dependent cytotoxicity and shape immune responses. Renal carcinoma cells often exploit complement regulators to resist elimination, and loss of CD46 may render these cells susceptible to complement-mediated lysis or alter their interaction with infiltrating T cells. Furthermore, the VHL-mutated background may synergize with CD46 loss to influence hypoxia-related pathways and tumor progression. This model thus offers a platform to investigate the crosstalk between complement inactivation, viral susceptibility, and cancer immunoevasion mechanisms.
This knockout cell pool supports diverse experimental applications, including functional dissection of complement regulation, evaluation of immune escape strategies in ccRCC, and mechanistic studies of viral entry. Representative assays encompass flow cytometry for CD46 surface loss confirmation, complement-mediated cytotoxicity testing, viral infection assays, and T-cell co-stimulation experiments. Researchers can employ these cells for drug target validation in complement-related disorders and for probing the role of CD46 in inflammatory signaling. For further details, please contact Ascent Research.
