The DNASE2 Knockout HGC-27 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the HGC-27 human gastric carcinoma cell line, engineered for loss-of-function studies of the DNASE2 gene. This polyclonal knockout pool provides a robust, heterogeneous model in which DNASE2 expression is disrupted via CRISPR/Cas9-mediated target-gene disruption, enabling functional interrogation of DNASE2 in a human epithelial cancer background. The product is suitable for a range of downstream applications, including biochemical, imaging, and functional assays, without requiring single-cell clonal isolation. As a polyclonal population, it preserves biological variability while offering stable knockout representation across the culture, supporting reproducible experimental designs in drug discovery and mechanistic research.
The parental HGC-27 cell line was established from a metastatic lymph node of a human gastric adenocarcinoma (undifferentiated) and serves as a widely used in vitro model for gastric cancer biology. HGC-27 cells exhibit epithelial morphology and are routinely applied to study tumor cell proliferation, metastasis, and drug response. Their origin from an undifferentiated adenocarcinoma provides a relevant cellular context for investigating aggressive gastric cancer phenotypes, including impaired apoptosis and altered innate immune signaling. The availability of a DNASE2-knockout derivative in this line enables direct exploration of lysosomal nuclease function in a genetically manipulable gastric cancer model, facilitating comparative studies with the isogenic wild-type HGC-27 parental cells.
DNASE2 encodes a lysosomal endonuclease that digests DNA from apoptotic cells or engulfed debris within the acidic lysosomal lumen. Its activity is regulated upstream by transcription factor EB (TFEB), interferon-gamma, and various cellular stress signals. DNASE2 interacts with lysosomal components such as LAMP1 and lysosomal proteases, maintaining efficient DNA clearance and preventing the accumulation of undigested DNA fragments. Mechanistically, DNASE2 functions to suppress aberrant activation of the cyclic GMP-AMP synthase (cGAS)?Cstimulator of interferon genes (STING) pathway; loss of DNASE2 leads to cytosolic escape of DNA, triggering cGAS, which synthesizes cGAMP, activating STING, TANK-binding kinase 1 (TBK1), and interferon regulatory factor 3 (IRF3), ultimately driving type I interferon and proinflammatory cytokine production. Thus, DNASE2 is a critical negative regulator of innate immune sensing of self-DNA.
In the HGC-27 gastric carcinoma context, DNASE2 knockout introduces a valuable perturbation for dissecting the interplay between lysosomal dysfunction and innate immune signaling in cancer. HGC-27 cells are derived from an undifferentiated adenocarcinoma, a subtype often associated with genomic instability and potential for DNA leakage. Disruption of DNASE2 in this background can unmask cGAS-STING pathway activation and its downstream consequences, including type I interferon responses that may modulate the tumor microenvironment and influence tumor cell-autonomous behaviors such as proliferation and apoptosis. This model thus provides a physiologically relevant platform to investigate how impaired DNA degradation contributes to inflammatory signaling in gastric cancer, with potential implications for understanding autoinflammatory complications and immune evasion mechanisms in epithelial malignancies.
This DNASE2 knockout polyclonal cell product supports diverse research applications, including the study of lysosomal DNA degradation, autoinflammatory diseases, systemic lupus erythematosus, anemia, and lysosomal storage disorders. Experimentally, it is suited for western blotting and RT-qPCR to confirm DNASE2 deficiency, immunofluorescence staining of lysosomal markers such as LAMP1, in vitro DNA degradation assays, and monitoring cGAS-STING pathway activation via phospho-IRF3 or IFN-beta expression. It also enables apoptosis assays and cytokine profiling to assess functional consequences of DNASE2 loss. These cells can be used for screening modulators of DNASE2 activity or for investigating the cGAS-STING axis in gastric cancer. For additional information, please contact Ascent Research.
