The DNASE2 Knockout Raji Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population in which the DNASE2 gene has been targeted for disruption. This mixed population derives from the Raji B lymphocyte host and is designed as a loss-of-function model to study the consequences of DNASE2 deficiency. The use of polyclonal cells provides a biologically relevant setting for functional assays without the clonal selection artifacts that can arise in single-cell-derived lines. This product is supplied as a ready-to-use polyclonal stock, enabling researchers to interrogate DNASE2-dependent pathways in a B cell context.
Raji is a suspension-adapted cell line originally established from a male patient with Burkitt’s lymphoma. The cells harbor a nonproductive Epstein-Barr virus (EBV) infection and exhibit surface immunoglobulin M expression, which makes them an extensively employed model for B cell receptor signaling, antigen presentation, and immune function studies. The EBV-positive background also offers a unique platform to examine viral-host interactions and lymphomagenesis. Raji cells are particularly amenable to transfection and CRISPR-based gene editing, facilitating the generation of knockout derivatives for mechanistic investigations.
DNASE2 encodes a lysosomal deoxyribonuclease that mediates the hydrolysis of double-stranded and single-stranded DNA in acidic environments. It plays an essential role in the clearance of nucleic acid waste derived from apoptotic cell debris and from DNA captured during autophagy. DNASE2 activity is regulated by the transcription factor TFEB, a master controller of lysosomal biogenesis, and is influenced by mTORC1-mediated nutrient sensing. Downstream, DNASE2-generated oligonucleotides suppress the cGAS-STING cytosolic DNA-sensing pathway, thereby preventing excessive type I interferon production. In the absence of DNASE2, undigested DNA accumulates in lysosomes, leading to chronic activation of innate immune sensors and autoinflammatory phenotypes. Representative pathway components that intersect with DNASE2 function include LC3, ATG genes, STING, cGAS, and various lysosomal hydrolases.
In Raji B lymphocytes, disruption of DNASE2 creates a relevant in vitro system to mimic aspects of DNASE2 deficiency-associated disorders, such as anemia and inflammatory arthritis. Given the centrality of B cells in adaptive immunity and their role in systemic autoimmune conditions like systemic lupus erythematosus, this model allows dissection of B cell-autonomous effects of defective DNA catabolism. The DNASE2 knockout Raji cells can be used to investigate how accumulated self-DNA triggers B cell activation, cytokine secretion, and autoreactive responses, thereby shedding light on the molecular pathogenesis of DNA-driven inflammation.
Researchers can apply this polyclonal knockout model in a variety of assays, including Western blotting to confirm loss of protein, RT-qPCR for transcript analysis, immunofluorescence for lysosomal localization studies, and DNA degradation assays to measure enzymatic activity. The cells are also suitable for flow cytometry-based phenotyping and multiplex cytokine profiling to assess inflammatory signatures. Drug screening campaigns targeting DNASE2-related pathways, as well as studies on lysosome-mediated DNA handling, can be performed. For additional information or to discuss custom experimental designs, please contact Ascent Research.
