The DNASE2 Knockout A2780 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the A2780 human ovarian cancer cell line, engineered to disrupt the endogenous DNASE2 gene. This polyclonal product provides a heterogeneous loss-of-function model for studying DNASE2-dependent DNA degradation and innate immune signaling, without clonal selection. It is suitable for applications requiring a population-level representation of DNASE2 deficiency, including functional genomics, pathway analysis, and drug response studies.
The parental A2780 cell line originates from an untreated ovarian endometrioid adenocarcinoma and is estrogen receptor-positive. It serves as a widely used model for ovarian adenocarcinoma research and drug sensitivity studies, particularly for assessing responses to platinum-based chemotherapeutics such as cisplatin and PARP inhibitors. These cells provide a relevant context for examining interactions between DNA damage, apoptosis, and immune activation within the tumor microenvironment.
DNASE2 encodes a lysosomal endonuclease that degrades DNA under acidic conditions, essential for clearing DNA from apoptotic cells and debris. Its expression is transcriptionally regulated by TFEB, a master regulator of lysosomal biogenesis, and is induced by inflammatory cytokines like TNF-?? and IL-1??. DNASE2 acts downstream of cellular stress signals to prevent self-DNA accumulation that would activate the cGAS-STING pathway. Upon DNASE2 loss, undigested DNA activates cGAS, generating cyclic GAMP to stimulate STING, leading to TBK1 phosphorylation of IRF3 and IFN-?? production. DNASE2 interacts with the mannose-6-phosphate receptor for lysosomal targeting and cooperates with cathepsins; it also functions in apoptosis-related DNA degradation, linking lysosomal activity to innate immunity.
In A2780 cells, disrupting DNASE2 impairs lysosomal DNA clearance, potentially leading to self-DNA accumulation and aberrant activation of the cGAS-STING pathway. This may trigger interferon responses and alter tumor microenvironment interactions, as described in the mechanistic summary. The polyclonal knockout population captures diverse editing events, enabling the study of heterogeneous loss-of-function phenotypes and their collective impact on apoptosis, autophagy, and innate immune signaling in an ovarian cancer context.
These cells are suitable for investigating lysosomal DNA degradation, innate immune activation in ovarian cancer, and chemotherapy-induced apoptosis and DNA clearance. Researchers can use Western blotting, RT-qPCR, immunofluorescence, TUNEL and Annexin V assays, phospho-STING detection, IFN-?? ELISA, flow cytometry, and drug sensitivity assays with cisplatin or PARP inhibitors. The model also supports tumor immunology studies focused on the cGAS-STING axis and downstream interferon regulatory factors. For additional information, please contact Ascent Research.
