OATP-H CRISPR Activation Plasmid (h): sc-404706-ACT

Human SLCO4C1 encodes OATP-H, an organic anion transporting polypeptide in the solute carrier (SLC) superfamily that mediates sodium-independent uptake of diverse endogenous metabolites and xenobiotic-like compounds across cellular membranes. By regulating cellular influx and distribution of amphipathic organic anions, OATP-H contributes to transporter-driven metabolic homeostasis and influences exposure of tissues to circulating small molecules. SLCO4C1 expression patterns and transporter activity intersect with pathways governing detoxification, cellular stress responses, and pharmacokinetic handling in barrier and excretory contexts. Altered SLCO4C1 regulation has been investigated in relation to renal and cardiometabolic phenotypes and as a modifier of tissue-specific susceptibility to chemical and inflammatory stressors.

OATP-H CRISPR Activation Plasmid (h) provides a targeted, non-destructive approach to upregulating endogenous SLCO4C1 expression without altering the underlying DNA sequence.

OATP-H CRISPR Activation Plasmid (h) is a three-plasmid synergistic activation mediator (SAM) system engineered for highly efficient, site-specific transcriptional upregulation of the SLCO4C1 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 SLCO4C1 transcriptional start site, where VP64, p65, and HSF1 act in concert to recruit transcriptional machinery and drive upregulation of endogenous OATP-H expression. Unlike nuclease-active Cas9, dCas9 does not introduce double-strand breaks or modify the genomic sequence, preserving the native SLCO4C1 locus and enabling the study of OATP-H-dependent transcriptional responses at the endogenous locus, making it a valuable tool for functional studies, target gene identification, and the modeling of OATP-H pathway restoration in tumor cells with silenced or reduced SLCO4C1 expression.

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