CRBN Knockout Cell Line (HEK 293)

The choice depends on whether you are studying CRBN (cereblon) in a complementary high-transfection-efficiency biochemistry platform — CRBN is the substrate receptor of the CRL4^CRBN E3 ubiquitin ligase and the molecular target of thalidomide, lenalidomide, pomalidomide, and the entire IMiD class and CRBN-recruiting PROTAC field. The Knockout line is the standard tool for asking whether CRBN is required for IMiD/molecular glue/PROTAC degrader activity — CRBN was identified as the thalidomide target and is the foundational molecular glue degrader receptor. Overexpression is useful for studying CRBN in heterologous expression contexts. For systematic CRBN biochemistry, the EDITGENE CRBN Knockout in HEK293 is a workhorse mechanistic platform — HEK293 supports systematic structure-function studies and high-throughput rescue mutant screening. This product complements the parallel CRBN Knockout in HeLa (also available); HEK293 is preferred for biochemistry and structure-function studies, HeLa for imaging-based and chemotherapy resistance studies. Rescue with wild-type or thalidomide-binding-pocket mutants (Y355A, W380A, W386A, W400A) enables systematic IMiD/molecular glue/PROTAC specificity testing. The knockout is a critical specificity tool for the entire CRBN-targeting therapeutic field including thalidomide, lenalidomide (Revlimid), pomalidomide (Pomalyst), iberdomide, mezigdomide, GSPT1 degraders (CC-90009), and CRBN-recruiting PROTACs (ARV-110, ARV-471, KT-474, NX-2127, DT2216).

Primary applications: • IMiD specificity: critical genetic control for thalidomide, lenalidomide (Revlimid), pomalidomide (Pomalyst), iberdomide, mezigdomide — these IMiDs should have no degrader activity in CRBN-null cells. • Molecular glue degrader specificity: CC-90009 (GSPT1 degrader), CC-885, and emerging CRBN-recruiting molecular glues. • CRBN-recruiting PROTAC specificity: ARV-110 (AR), ARV-471 (ER), KT-474 (IRAK4), NX-2127 (BTK), DT2216 (BCL-XL) specificity testing. • Systematic mutation screening: HEK293's high transfection efficiency supports systematic Y355A, W380A, W386A, W400A mutant rescue analysis. EDITGENE recommends this HEK293-based model as the gold-standard biochemistry platform for the entire CRBN-targeted therapeutic field; the parallel CRBN Knockout in HeLa (also available) is preferred for imaging studies.

Yes, and rescue experiments are uniquely powerful for IMiD/molecular glue/PROTAC research: • Construct design: use a codon-modified CRBN sequence with a small C-terminal tag (FLAG, HA). CRBN has N-terminal Lon protease-like domain, helical-bundle domain, and C-terminal thalidomide-binding domain (TBD) with the critical tri-tryptophan/Y pocket — preserve all elements. • Thalidomide-binding-pocket mutant rescue: ⭐⭐ Y355A, W380A, W386A, W400A mutations abolish IMiD binding — gold-standard specificity control for the entire CRBN-targeted therapeutic field. • IMiD resistance mutation rescue: clinical IMiD-resistant patient CRBN mutations enable resistance mechanism studies. • DDB1-binding-deficient rescue: N-terminal CRBN mutations disrupt CRL4 complex assembly. • Functional readout: rescue should restore IKZF1, IKZF3, CK1α, GSPT1 degradation upon IMiD/molecular glue treatment; thalidomide-binding-pocket mutants should be insensitive to all CRBN-recruiting compounds. HEK293 transduces efficiently with lentivirus and supports stable rescue line generation for systematic CRBN mutant screening.