The MTAP Knockout Raji Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population of the Raji B lymphoblastoid cell line, designed for loss-of-function studies of methylthioadenosine phosphorylase (MTAP). This heterogeneous pool offers a robust model for investigating MTAP-dependent pathways without the biases of clonal selection. CRISPR/Cas9-mediated gene disruption ensures efficient target inactivation across the population.
The Raji cell line, established from an EBV-positive Burkitt’s lymphoma, serves as a classic model for B-cell biology, lymphomagenesis, and immune response research. Its B lymphocyte origin and well-characterized signaling networks make it particularly suitable for genetic manipulation. The Raji background provides a clinically relevant context for studying MTAP deletion in hematological malignancies, where loss of the CDKN2A/MTAP locus is common.
MTAP catalyzes the phosphorolysis of methylthioadenosine (MTA) in the methionine salvage pathway, linking polyamine metabolism to purine salvage. Knockout of MTAP results in MTA accumulation, which directly inhibits the PRMT5/WDR77 methyltransferase complex. This inhibition diminishes symmetric dimethylarginine (SDMA) marks on downstream substrates, including splicing factors, thereby perturbing RNA processing and gene expression. Transcription factors c-Myc and E2F1 regulate MTAP expression, and its genomic deletion with CDKN2A is frequent in cancer. The resulting dysregulation of S-adenosylmethionine and ornithine decarboxylase creates a synthetic lethal vulnerability with PRMT5 or MAT2A inhibition.
In the Raji B-cell lymphoma environment, MTAP loss mimics the genetic landscape of aggressive lymphoid cancers. This polyclonal knockout model is instrumental for dissecting the synthetic lethality between MTAP deficiency and PRMT5/MAT2A dependencies, which are actively pursued as therapeutic targets. Moreover, the population-based knockout reflects tumor heterogeneity, enabling studies on how MTAP inactivation affects B-cell proliferation, apoptosis, and response to immunomodulatory signals.
These polyclonal knockout cells are suitable for synthetic lethality screens with PRMT5 inhibitors (e.g., GSK3326595) or MAT2A inhibitors (e.g., AG-270), MTA quantification via LC-MS, PRMT5 activity assays, and western blotting for SDMA. Additional applications include drug sensitivity testing, RNA-seq for splicing analysis, and metabolic profiling. The model also supports polyamine metabolism and epigenetic regulation studies. For further details, please contact Ascent Research.
