UGT1A1 Lentiviral Activation Particles (h): sc-401190-LAC

UGT1A1 encodes UDP-glucuronosyltransferase 1A1, a microsomal phase II detoxification enzyme that catalyzes glucuronidation of bilirubin and diverse endogenous and xenobiotic substrates in the endoplasmic reticulum. By converting lipophilic compounds into more water-soluble glucuronides, UGT1A1 supports hepatic clearance and coordinates with broader drug metabolism pathways, including cytochrome P450–linked biotransformation and transporter-mediated efflux. Variation in UGT1A1 expression or activity is a key determinant of bilirubin homeostasis and interindividual differences in metabolism of drugs and environmental chemicals, with strong relevance to pharmacogenomics and liver function research. Dysregulation of glucuronidation capacity is also studied in the context of metabolic stress and hepatobiliary disease mechanisms.

UGT1A1 Lentiviral Activation Particles (h) address this need by packaging the complete synergistic activation mediator (SAM) transcriptional activation system into transduction-ready, high-titer lentiviral particles, enabling efficient UGT1A1 upregulation across a broader range of human cell types.

UGT1A1 Lentiviral Activation Particles (h) 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 UGT1A1 transcriptional start site, where VP64, p65, and HSF1 act cooperatively to recruit endogenous transcriptional machinery and drive sustained upregulation of endogenous UGT1A1 expression. The use of nuclease-inactive dCas9 avoids the introduction of double-strand DNA breaks and preserves the native UGT1A1 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.