Angptl4 CRISPR Activation Plasmid (h): sc-401369-ACT

ANGPTL4 encodes angiopoietin-like 4 (Angptl4), a secreted glycoprotein induced by nutrient and oxygen cues that modulates lipid handling and vascular biology. Angptl4 inhibits lipoprotein lipase to regulate triglyceride-rich lipoprotein metabolism and intersects with metabolic programs controlled by PPAR signaling, linking adipose and hepatic responses to fasting and inflammation. In the extracellular milieu, it can influence endothelial behavior, barrier function, and extracellular matrix remodeling, connecting metabolic state to tissue homeostasis. Dysregulated ANGPTL4 expression has been associated with metabolic disorders, inflammatory microenvironments, and tumor-associated processes, making it a useful node for mechanistic studies of lipid flux and vascular responses.

Angptl4 CRISPR Activation Plasmid (h) provides a targeted, non-destructive approach to upregulating endogenous ANGPTL4 expression without altering the underlying DNA sequence.

Angptl4 CRISPR Activation Plasmid (h) is a three-plasmid synergistic activation mediator (SAM) system engineered for highly efficient, site-specific transcriptional upregulation of the ANGPTL4 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 ANGPTL4 transcriptional start site, where VP64, p65, and HSF1 act in concert to recruit transcriptional machinery and drive upregulation of endogenous Angptl4 expression. Unlike nuclease-active Cas9, dCas9 does not introduce double-strand breaks or modify the genomic sequence, preserving the native ANGPTL4 locus and enabling the study of Angptl4-dependent transcriptional responses at the endogenous locus, making it a valuable tool for functional studies, target gene identification, and the modeling of Angptl4 pathway restoration in tumor cells with silenced or reduced ANGPTL4 expression.

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