The APOBEC3C Knockout NCI-H1703 Polyclonal Cells comprise a CRISPR/Cas9-edited polyclonal cell population featuring targeted disruption of the APOBEC3C gene in the NCI-H1703 human lung squamous cell carcinoma cell line. This product provides a loss-of-function model for studying APOBEC3C biology without introducing specific editing patterns or clonal selection, enabling population-level analysis of gene function. The polyclonal format preserves the heterogeneous responses typical of CRISPR/Cas9-mediated gene disruption, offering a robust tool for examining APOBEC3C-dependent processes in a physiologically relevant cancer context.
The NCI-H1703 host cell line is derived from a lung squamous cell carcinoma of a 52-year-old male smoker and serves as an established model for non-small cell lung cancer (NSCLC). These cells exhibit characteristics of squamous differentiation and carry genetic alterations frequently observed in smoking-associated lung cancers. As a widely used research platform, NCI-H1703 cells support investigations into tumor biology, therapeutic resistance, and mutational landscapes, particularly those linked to APOBEC family enzymes. Their well-characterized background makes them suitable for studying the interplay between genomic instability and antiviral defense mechanisms.
APOBEC3C is a DNA cytidine deaminase that restricts retroviruses and retrotransposons by catalyzing C-to-U mutations in single-stranded DNA, leading to G-to-A hypermutation and viral DNA degradation. Its expression is activated by interferon-alpha and interferon-gamma through transcription factors IRF1, IRF3, NF-??B, and STAT1, linking it to innate antiviral immunity. APOBEC3C interacts with viral Vif proteins and paralogs APOBEC3F and APOBEC3G, and its off-target activity on host genomic DNA at replication forks generates uracil lesions processed by uracil-DNA glycosylase (UNG) and APE1, contributing to DNA damage and cancer-associated mutagenesis. Mechanistically, APOBEC3C functions downstream of interferon receptors (IFNAR), engaging JAK1/TYK2 kinases and STAT1/STAT2/IRF9 complexes to promote transcription of restriction factors, while its deaminase activity directly mutagenizes ssDNA substrates.
In the NCI-H1703 model, APOBEC3C knockout provides a critical tool for dissecting APOBEC-mediated mutagenesis in lung squamous cell carcinoma, a cancer type frequently exhibiting APOBEC mutational signatures. This system allows researchers to evaluate how loss of APOBEC3C affects mutation burden, DNA damage response pathways, and sensitivity to chemotherapeutics or targeted agents. The knockout cells also enable study of interferon-driven antiviral responses in a cancer cell environment, bridging innate immunity and tumor biology. By abolishing APOBEC3C function, this model helps clarify its dual role in host defense and genomic instability, particularly in the context of smoking-associated DNA damage.
These polyclonal knockout cells are ideally suited for a range of research applications, including analysis of APOBEC mutational signatures via next-generation sequencing, assessment of viral restriction using HIV-1 single-cycle infectivity assays, and evaluation of DNA damage by comet assays or immunofluorescence staining of ??H2AX. Western blotting and RT-qPCR can confirm target disruption, while cytidine deaminase activity assays directly measure enzymatic function. Cell viability and proliferation assays under DNA-damaging conditions further elucidate APOBEC3C??s role in genomic maintenance. For additional information on this product or to discuss customized solutions, please contact Ascent Research.
