ADAMTS-1 CRISPR Activation Plasmid (h): sc-402048-ACT

ADAMTS1 encodes ADAMTS-1, a secreted zinc-dependent metalloproteinase that remodels the extracellular matrix by cleaving proteoglycans such as versican and aggrecan. Through regulation of matrix turnover, cell–matrix adhesion, and pericellular signaling, ADAMTS-1 influences tissue morphogenesis, wound responses, inflammation, and vascular biology, including angiogenic and ovulatory processes. ADAMTS1 activity intersects with pathways governed by cytokines and growth factors, shaping stromal–epithelial interactions and cell migration programs. Dysregulated ADAMTS1 expression has been linked to pathological extracellular matrix remodeling observed across cancer invasion/metastasis contexts, fibrotic and inflammatory conditions, and cardiovascular and reproductive biology phenotypes.

ADAMTS-1 CRISPR Activation Plasmid (h) provides a targeted, non-destructive approach to upregulating endogenous ADAMTS1 expression without altering the underlying DNA sequence.

ADAMTS-1 CRISPR Activation Plasmid (h) is a three-plasmid synergistic activation mediator (SAM) system engineered for highly efficient, site-specific transcriptional upregulation of the ADAMTS1 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 ADAMTS1 transcriptional start site, where VP64, p65, and HSF1 act in concert to recruit transcriptional machinery and drive upregulation of endogenous ADAMTS-1 expression. Unlike nuclease-active Cas9, dCas9 does not introduce double-strand breaks or modify the genomic sequence, preserving the native ADAMTS1 locus and enabling the study of ADAMTS-1-dependent transcriptional responses at the endogenous locus, making it a valuable tool for functional studies, target gene identification, and the modeling of ADAMTS-1 pathway restoration in tumor cells with silenced or reduced ADAMTS1 expression.

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