OATP-C CRISPR Activation Plasmid (h): sc-402898-ACT

SLCO1B1 encodes the human organic anion transporting polypeptide OATP-C (OATP1B1), a multispecific uptake transporter enriched in hepatocytes that mediates sodium-independent influx of bile acids, bilirubin conjugates, steroid hormone metabolites, thyroid hormones, and diverse xenobiotics. By controlling sinusoidal import into liver cells, OATP-C influences hepatic clearance, enterohepatic recycling, and systemic exposure to endogenous metabolites and small-molecule substrates. SLCO1B1 activity intersects with detoxification and metabolic pathways coordinated with phase I/II enzymes and ABC efflux transporters, shaping transporter–enzyme interplay in pharmacokinetic networks. Genetic variation or dysregulated expression is associated with altered drug disposition and susceptibility to transporter-mediated adverse reactions, and is studied in the context of liver function, hyperbilirubinemia, and drug–drug interaction mechanisms.

OATP-C CRISPR Activation Plasmid (h) provides a targeted, non-destructive approach to upregulating endogenous SLCO1B1 expression without altering the underlying DNA sequence.

OATP-C CRISPR Activation Plasmid (h) is a three-plasmid synergistic activation mediator (SAM) system engineered for highly efficient, site-specific transcriptional upregulation of the SLCO1B1 locus in human cell lines. The system is built around a catalytically inactive Cas9 (dCas9) carrying two inactivating mutations (D10A and N863A) that eliminate nuclease activity while preserving DNA binding. This dCas9 is fused to VP64, a potent transcriptional activator, and is co-expressed with a blasticidin resistance gene for selection. The second plasmid encodes the MS2-p65-HSF1 fusion protein, a secondary activator complex that works in concert with dCas9-VP64, alongside a hygromycin resistance gene. The third plasmid encodes a target-specific 20 nt sgRNA fused to two MS2 RNA aptamers that recruit the MS2-p65-HSF1 complex to the activation site, accompanied by a puromycin resistance gene. The three plasmids are delivered at a 1:1:1 mass ratio for balanced expression of all system components.

Once assembled at the target locus, the SAM complex binds within approximately 200 bp upstream of the SLCO1B1 transcriptional start site, where VP64, p65, and HSF1 act in concert to recruit transcriptional machinery and drive upregulation of endogenous OATP-C expression. Unlike nuclease-active Cas9, dCas9 does not introduce double-strand breaks or modify the genomic sequence, preserving the native SLCO1B1 locus and enabling the study of OATP-C-dependent transcriptional responses at the endogenous locus, making it a valuable tool for functional studies, target gene identification, and the modeling of OATP-C pathway restoration in tumor cells with silenced or reduced SLCO1B1 expression.

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