SUR-2 CRISPR Activation Plasmid (h): sc-401399-ACT

ABCC9 encodes the sulfonylurea receptor 2 (SUR-2), a regulatory subunit of ATP-sensitive potassium (KATP) channels that couples cellular energetic state to membrane excitability. By assembling with inward-rectifier potassium channel subunits to form functional KATP complexes, SUR-2 helps tune potassium conductance in response to nucleotides and pharmacologic ligands, influencing vascular smooth muscle tone and cardiac electrical activity. This signaling axis integrates metabolic sensing with ion homeostasis and stress responsiveness, affecting processes such as vasodilation, action potential dynamics, and protection during energetic challenge. Genetic variation or dysregulation of ABCC9 has been linked to cardiovascular and systemic phenotypes involving excitability and tissue perfusion, supporting its relevance for mechanistic studies of channel regulation and cardiometabolic biology.

SUR-2 CRISPR Activation Plasmid (h) provides a targeted, non-destructive approach to upregulating endogenous ABCC9 expression without altering the underlying DNA sequence.

SUR-2 CRISPR Activation Plasmid (h) is a three-plasmid synergistic activation mediator (SAM) system engineered for highly efficient, site-specific transcriptional upregulation of the ABCC9 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 ABCC9 transcriptional start site, where VP64, p65, and HSF1 act in concert to recruit transcriptional machinery and drive upregulation of endogenous SUR-2 expression. Unlike nuclease-active Cas9, dCas9 does not introduce double-strand breaks or modify the genomic sequence, preserving the native ABCC9 locus and enabling the study of SUR-2-dependent transcriptional responses at the endogenous locus, making it a valuable tool for functional studies, target gene identification, and the modeling of SUR-2 pathway restoration in tumor cells with silenced or reduced ABCC9 expression.

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