SARM1 Knockout Cell Line (HEK293)

The choice depends on whether you are studying SARM1's role as the central executioner of axon degeneration or its enzymatic activity as a NAD⁺ glycohydrolase. The Knockout line is the standard tool for asking whether SARM1 is required for activation-induced NAD⁺ depletion — SARM1 is a dormant NAD⁺ hydrolase that, upon activation by NMN/NAD⁺ ratio increase or injury, catalyzes catastrophic NAD⁺ destruction triggering Wallerian axon degeneration. Overexpression is useful for studying constitutively active SARM1 mutants (E642A) or testing inhibitor specificity. For SARM1 research, the EDITGENE Knockout in HEK293 is the standard mechanistic platform — HEK293 has been extensively used for SARM1 biochemistry, structure-function studies, and inhibitor screening. Rescue with wild-type, catalytically-dead (E642A or constitutively active depending on the mutation), or autoinhibition-released SARM1 enables comprehensive mechanism studies. SARM1 is a major therapeutic target for chemotherapy-induced peripheral neuropathy, diabetic neuropathy, and other axonopathies — multiple SARM1 inhibitors are in clinical development.

Primary applications: • NAD⁺ hydrolase activity: cellular NAD⁺ depletion kinetics following SARM1 activation triggers (NMN treatment, vincristine, axon injury mimics). • Mechanism of activation studies: NMN/NAD⁺ ratio manipulation, ARM domain conformational dynamics, and TIR domain dimerization analysis. • Chemotherapy-induced neuropathy modeling: vincristine, paclitaxel, and bortezomib-induced cellular phenotypes given SARM1's central role in chemotherapy-induced peripheral neuropathy. • Inhibitor specificity: critical genetic control for SARM1 inhibitors in clinical development (NB-101 and related molecules) for neurodegenerative disease. EDITGENE recommends this model for researchers investigating axon degeneration mechanisms, NAD⁺ biology, chemotherapy-induced neuropathy, and SARM1-targeted therapeutic development.

Yes. SARM1 rescue experiments are well-established for axon degeneration research: • Construct design: use a codon-modified SARM1 sequence with a small C-terminal tag (FLAG, HA). SARM1 contains an N-terminal mitochondrial targeting sequence/ARM autoinhibitory domain, central SAM dimerization domain, and C-terminal TIR catalytic domain — all essential for regulated activation. • Catalytically-dead rescue: the E642A mutation in the TIR domain abolishes NAD⁺ hydrolase activity and is the standard specificity control. • Constitutively active rescue: ARM domain mutations or deletions release autoinhibition, generating constitutively active SARM1 useful for gain-of-function studies. • Functional readout: rescue should restore activation-induced NAD⁺ depletion measured by NAD⁺/NADH ratio assays following NMN treatment or other activation triggers. HEK293 transduces efficiently with lentivirus and is the standard heterologous expression background for SARM1 biochemistry.