The FOLR1 Knockout Raji Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the Raji B lymphocyte line, featuring targeted disruption of the FOLR1 gene encoding folate receptor alpha (FR??). This format provides a heterogeneous pool of loss-of-function mutations, avoiding clonal bias and enabling robust population-level studies of folate biology and associated pathways.
The Raji host cell line, derived from a Nigerian Burkitt lymphoma patient, is an EBV-positive immortalized B lymphocyte model widely used in B cell biology and immunology. These suspension cells proliferate rapidly and exhibit high folate demand, making them particularly relevant for studying folate-dependent nucleotide metabolism. Raji cells retain key B cell surface markers and signaling pathways, enabling integration of metabolic studies with B cell receptor and viral latency research.
FOLR1 encodes a glycosylphosphatidylinositol-anchored receptor that mediates high-affinity folate uptake via clathrin-independent, caveolin-1-associated endocytosis. Following internalization, folates feed the one-carbon cycle, driving purine and thymidylate biosynthesis and S-adenosylmethionine production. Expression is transcriptionally regulated by Sp1 and ESR1, and is responsive to all-trans retinoic acid and folate status. Downstream, FOLR1 supports the activity of MTHFR, MTR, and TYMS, linking extracellular folate availability to nucleotide synthesis and methylation potential.
In the Raji context, FOLR1 knockout cripples high-affinity folate uptake, starving cells of nucleotides for DNA replication and repair. This renders the polyclonal population hypersensitive to antifolate drugs like methotrexate and concurrently reduces global DNA methylation. The EBV-positive background adds clinical significance, mirroring metabolic vulnerabilities of aggressive B cell lymphomas.
Applications include folate uptake kinetics, methotrexate dose?Cresponse profiling, and targeted drug delivery validation using FR??-directed conjugates. The polyclonal cells support pooled CRISPR screens, nucleotide pool quantification by LC-MS, DNA methylation analyses, and functional assays examining B cell signaling cross-talk. Researchers investigating antifolate resistance, therapeutic antibody development, or one-carbon metabolism in malignancy will find this model valuable. For additional technical information or custom orders, please contact Ascent Research.
