SOSTDC1 CRISPR Activation Plasmid (h): sc-403398-ACT

Human SOSTDC1 encodes sclerostin domain-containing protein 1, a secreted antagonist of BMP and Wnt signaling that modulates receptor–ligand interactions to constrain pathway activity. By dampening BMP-driven SMAD signaling and influencing β-catenin–dependent transcription, SOSTDC1 contributes to regulation of developmental patterning, osteogenic differentiation, and tissue homeostasis. Altered SOSTDC1 expression has been reported in multiple contexts of dysregulated growth-factor signaling, including cancers and fibrotic or remodeling-associated states, where BMP/Wnt balance impacts proliferation, differentiation, and extracellular matrix programs. As a soluble pathway regulator, it is frequently studied in paracrine signaling, epithelial–mesenchymal crosstalk, and microenvironment-dependent phenotypes.

SOSTDC1 CRISPR Activation Plasmid (h) provides a targeted, non-destructive approach to upregulating endogenous SOSTDC1 expression without altering the underlying DNA sequence.

SOSTDC1 CRISPR Activation Plasmid (h) is a three-plasmid synergistic activation mediator (SAM) system engineered for highly efficient, site-specific transcriptional upregulation of the SOSTDC1 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 SOSTDC1 transcriptional start site, where VP64, p65, and HSF1 act in concert to recruit transcriptional machinery and drive upregulation of endogenous SOSTDC1 expression. Unlike nuclease-active Cas9, dCas9 does not introduce double-strand breaks or modify the genomic sequence, preserving the native SOSTDC1 locus and enabling the study of SOSTDC1-dependent transcriptional responses at the endogenous locus, making it a valuable tool for functional studies, target gene identification, and the modeling of SOSTDC1 pathway restoration in tumor cells with silenced or reduced SOSTDC1 expression.

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