TDO2 Lentiviral Activation Particles (h2): sc-402482-LAC-2

Human TDO2 (tryptophan 2,3-dioxygenase) encodes a heme-dependent enzyme that catalyzes the first and rate-limiting step of tryptophan catabolism through the kynurenine pathway, thereby regulating cellular tryptophan availability and downstream production of immunomodulatory and neuroactive metabolites. TDO2 activity links nutrient sensing and hepatic metabolic homeostasis to redox balance and signaling networks influenced by kynurenines, with consequences for immune regulation, stress responses, and neurotransmitter precursor flux. Dysregulated TDO2 expression or pathway output has been implicated in cancer immune evasion, inflammatory conditions, and neuropsychiatric or neurodegenerative disease contexts where altered tryptophan–kynurenine metabolism is observed. Gene editing of TDO2 supports mechanistic studies of metabolic reprogramming, kynurenine-dependent signaling, and interactions between tumor cells, hepatocytes, and immune cells in relevant human cell models.

TDO2 Lentiviral Activation Particles (h2) address this need by packaging the complete synergistic activation mediator (SAM) transcriptional activation system into transduction-ready, high-titer lentiviral particles, enabling efficient TDO2 upregulation across a broader range of human cell types.

TDO2 Lentiviral Activation Particles (h2) 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 TDO2 transcriptional start site, where VP64, p65, and HSF1 act cooperatively to recruit endogenous transcriptional machinery and drive sustained upregulation of endogenous TDO2 expression. The use of nuclease-inactive dCas9 avoids the introduction of double-strand DNA breaks and preserves the native TDO2 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.