Somatostatin CRISPR Activation Plasmid (h): sc-400280-ACT

Human SST encodes somatostatin, a peptide hormone broadly expressed in the nervous system and endocrine tissues that suppresses secretion of growth hormone, insulin, glucagon, and multiple gastrointestinal hormones. Somatostatin signals primarily through G protein–coupled somatostatin receptors (SSTR1–SSTR5), engaging Gi/o-mediated inhibition of adenylyl cyclase, modulation of ion channels, and downstream MAPK and PI3K pathway regulation to tune excitability, secretion, and cellular proliferation. In neuroendocrine and pancreatic contexts, SST contributes to paracrine control of islet hormone release and stress-responsive neuroendocrine signaling. Dysregulated somatostatin signaling is relevant to studies of metabolic homeostasis, neuroendocrine differentiation, and hormone-driven disease biology, including models of pancreatic islet dysfunction and neuroendocrine tumor phenotypes.

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

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

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