The IFIT1 Knockout HCT 116 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the HCT 116 human colorectal carcinoma line, with disruption of the IFIT1 gene to generate a loss-of-function model. This heterogeneous pool of edited alleles provides robust IFIT1 deficiency without single-cell cloning, enabling investigation of antiviral innate immunity and interferon signaling in an endogenous cellular context.
The HCT 116 cell line, originating from a male colon cancer patient, is a well-characterized human colorectal carcinoma model harboring a KRAS G13D mutation, MLH1 deficiency, and microsatellite instability (MSI). These epithelial cells demonstrate rapid proliferation, intact barrier function, and well-defined apoptotic pathways, making them suitable for studying cancer biology, signal transduction, and host-pathogen interactions. Their genetic background offers a clinically relevant platform to explore the intersection of antiviral immunity and tumor biology.
IFIT1 (Interferon-Induced Protein with Tetratricopeptide Repeats 1) is a critical antiviral effector induced by type I and III interferons through the JAK-STAT pathway. Interferon binding to IFNAR1/2 receptors activates JAK1 and TYK2, leading to STAT1/STAT2 phosphorylation and formation of the ISGF3 complex with IRF9, which translocates to the nucleus to drive transcription. Concurrently, cytosolic sensors RIG-I and MDA5 detect viral RNA and signal via MAVS and TBK1 to phosphorylate IRF3 and IRF7, further enhancing IFIT1 expression. IFIT1 functions as a sensor of 5′-triphosphate RNA, a molecular signature of many viruses, and directly binds the eIF3 translation initiation complex to inhibit protein synthesis, thereby restricting viral replication. IFIT1 cooperates with its paralogs IFIT2 and IFIT3, forming complexes that potentiate antiviral activity. Knockout of IFIT1 is expected to impair these downstream antiviral mechanisms and may disrupt interferon-mediated signaling feedback.
In the HCT 116 colorectal carcinoma background, IFIT1 knockout provides a valuable model to dissect the crosstalk between antiviral innate immunity and cancer-associated pathways. These interferon-responsive cells permit analysis of how IFIT1 loss alters interferon-induced growth inhibition, apoptosis, and immune signaling in epithelial tumor cells. Moreover, the MSI status and KRAS G13D mutation may influence cellular responses to viral mimicry or oncolytic virus therapy, aiding in the identification of tumor-selective vulnerabilities. The polyclonal nature of the knockout population reduces clonal artifacts and better represents the heterogeneous response typical of tumor cell populations.
This IFIT1 knockout HCT 116 polyclonal cell pool is suitable for a wide range of experimental assays, including western blotting, RT-qPCR, and RNA-seq for expression profiling; flow cytometry for assessing interferon response markers; viral replication and interferon response assays; and apoptosis, viability, and colony formation studies. It also supports drug sensitivity testing targeting JAK-STAT pathway components or innate immune sensors. For further information or technical support, please contact Ascent Research.
