The ISOC2 Knockout A-549 Polyclonal Cells offer a CRISPR/Cas9-edited polyclonal knockout population in the A-549 human lung adenocarcinoma cell line. This product provides a genetically heterogeneous pool of cells with target-gene disruption, enabling researchers to investigate gene function without the constraints of single-cell clonal selection. The knockout has been introduced using CRISPR/Cas9-mediated genome editing to impair ISOC2 expression, generating a loss-of-function model suitable for functional genomics and metabolic studies.
The A-549 cell line is an established epithelial model derived from a human non-small cell lung carcinoma, widely employed in cancer biology and drug discovery. These adherent cells retain characteristics of alveolar basal epithelial cells and are commonly used to study oncogenic signaling, metabolic reprogramming, and therapeutic responses in lung adenocarcinoma. Their robust growth and well-characterized transcriptome make them a reliable platform for CRISPR-based gene manipulation.
ISOC2 encodes a putative hydrolase that is predicted to catalyze amide bond hydrolysis, potentially participating in protein deamidation and nucleotide metabolism. Substrate metabolites and a zinc ion cofactor are likely involved in its catalytic mechanism. In the cellular signaling network, ISOC2 is regulated by the transcription factors HIF1A and MYC, both of which are central to metabolic adaptation in cancer. Disruption of ISOC2 may impact downstream targets such as intracellular NAD+ levels and pyrimidine nucleotide pools, processes that are dependent on pathway components including NAMPT, NNMT, and NMNAT1. Consequently, ISOC2 is thought to contribute to the maintenance of NAD+ homeostasis and nucleotide balance, which are critical for cell proliferation and survival.
In A-549 cells, ISOC2 knockout presents a physiologically relevant model for probing metabolic dependencies in non-small cell lung cancer. Given that HIF1A and MYC are frequently activated in lung adenocarcinomas, ISOC2 may serve as a downstream effector linking these oncogenic drivers to NAD+ metabolism and pyrimidine biosynthesis. The loss of ISOC2 function in this context can disrupt the delicate metabolic equilibrium, potentially impairing anabolic processes required for rapid cell growth and revealing targetable vulnerabilities within the NAD+ and nucleotide synthesis pathways.
Researchers can employ this polyclonal knockout population to perform functional characterization of ISOC2 in lung cancer metabolism, including assays such as Western blotting and RT-qPCR to confirm gene disruption and assess compensatory pathways. NAD+/NADH assays and metabolomics profiling can quantify metabolic perturbations, while cell viability and apoptosis assays allow evaluation of the knockout??s impact on cell proliferation and death. This model is ideal for drug target validation studies that seek to exploit metabolic weaknesses in NSCLC. For further technical details or to inquire about custom modifications, please contact Ascent Research.
