MRP1 CRISPR Activation Plasmid (h): sc-400456-ACT

ABCC1 encodes the human multidrug resistance–associated protein 1 (MRP1), an ATP-binding cassette transporter that exports a broad range of organic anions, xenobiotic conjugates, and endogenous metabolites across the plasma membrane. MRP1 couples ATP hydrolysis to efflux of glutathione, glucuronide, and sulfate conjugates, influencing cellular redox homeostasis, inflammatory mediator handling, and pharmacologic detoxification. Through modulation of intracellular substrate availability, ABCC1 activity interfaces with oxidative stress responses and xenobiotic metabolism pathways. Dysregulated ABCC1/MRP1 expression has been associated with altered drug disposition and resistance phenotypes in cancer and with disease contexts involving barrier transport and chronic inflammation.

MRP1 CRISPR Activation Plasmid (h) provides a targeted, non-destructive approach to upregulating endogenous ABCC1 expression without altering the underlying DNA sequence.

MRP1 CRISPR Activation Plasmid (h) is a three-plasmid synergistic activation mediator (SAM) system engineered for highly efficient, site-specific transcriptional upregulation of the ABCC1 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 ABCC1 transcriptional start site, where VP64, p65, and HSF1 act in concert to recruit transcriptional machinery and drive upregulation of endogenous MRP1 expression. Unlike nuclease-active Cas9, dCas9 does not introduce double-strand breaks or modify the genomic sequence, preserving the native ABCC1 locus and enabling the study of MRP1-dependent transcriptional responses at the endogenous locus, making it a valuable tool for functional studies, target gene identification, and the modeling of MRP1 pathway restoration in tumor cells with silenced or reduced ABCC1 expression.

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