CHAC1 Lentiviral Activation Particles (m): sc-427280-LAC

Mouse Chac1 encodes CHAC1, a cytosolic γ-glutamyl cyclotransferase that degrades glutathione and links redox homeostasis to cellular stress responses. CHAC1 is induced downstream of the unfolded protein response, particularly the PERK–eIF2α–ATF4 branch, and can contribute to oxidative stress, altered amino acid metabolism, and regulated cell death programs. Through modulation of intracellular glutathione pools, CHAC1 influences ferroptosis susceptibility, mitochondrial stress signaling, and inflammatory transcriptional outputs. Dysregulated CHAC1 expression has been associated with contexts of ER stress and neurodegeneration, ischemic and metabolic stress, and tumor biology, making it a useful node for mechanistic studies in stress-adaptation pathways.

CHAC1 Lentiviral Activation Particles (m) address this need by packaging the complete synergistic activation mediator (SAM) transcriptional activation system into transduction-ready, high-titer lentiviral particles, enabling efficient Chac1 upregulation across a broader range of human cell types.

CHAC1 Lentiviral Activation Particles (m) deliver all functional components of the synergistic activation mediator (SAM) system via lentiviral transduction. The system comprises three particle preparations co-transduced into target cells: one encoding catalytically inactive dCas9 (D10A and N863A mutations) fused to the VP64 transactivation domain with a blasticidin resistance gene; one encoding the MS2-p65-HSF1 fusion protein with a hygromycin resistance gene; and one encoding a target-specific 20 nt sgRNA fused to two MS2 RNA aptamers with a puromycin resistance gene. Following lentiviral transduction and genomic integration of the expression cassettes, the SAM components are stably expressed and assemble at the target locus within the proximal promoter region upstream of the Chac1 transcriptional start site, where VP64, p65, and HSF1 act cooperatively to recruit endogenous transcriptional machinery and drive sustained upregulation of endogenous CHAC1 expression. The use of nuclease-inactive dCas9 avoids the introduction of double-strand DNA breaks and preserves the native Chac1 genomic locus and regulatory architecture.

The lentiviral format offers several practical advantages: stable genomic integration supports heritable activation across cell divisions; high-titer particle preparations eliminate the need for in-house viral production; and compatibility with primary, non-dividing, and transfection-resistant cell types expands experimental accessibility. Successful transduction can be confirmed and enriched through triple antibiotic selection using puromycin, hygromycin, and blasticidin.

For Research Use Only. Not Intended for Diagnostic or Therapeutic Use.