Multimerin-1 CRISPR Activation Plasmid (h): sc-404741-ACT

MMRN1 encodes multimerin-1, a large disulfide-linked, multimeric glycoprotein stored in platelet α-granules and endothelial Weibel–Palade bodies and released upon cellular activation. Multimerin-1 localizes to the extracellular matrix and platelet surface, where it supports platelet adhesion and stabilization of hemostatic responses through interactions with coagulation- and matrix-associated partners. This biology links MMRN1 to pathways governing platelet degranulation, vascular homeostasis, and thrombus formation under shear. Altered MMRN1 expression or distribution has been investigated in bleeding and thrombotic phenotypes and as a marker of platelet/endothelial activation in inflammatory and vascular disease contexts.

Multimerin-1 CRISPR Activation Plasmid (h) provides a targeted, non-destructive approach to upregulating endogenous MMRN1 expression without altering the underlying DNA sequence.

Multimerin-1 CRISPR Activation Plasmid (h) is a three-plasmid synergistic activation mediator (SAM) system engineered for highly efficient, site-specific transcriptional upregulation of the MMRN1 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 MMRN1 transcriptional start site, where VP64, p65, and HSF1 act in concert to recruit transcriptional machinery and drive upregulation of endogenous Multimerin-1 expression. Unlike nuclease-active Cas9, dCas9 does not introduce double-strand breaks or modify the genomic sequence, preserving the native MMRN1 locus and enabling the study of Multimerin-1-dependent transcriptional responses at the endogenous locus, making it a valuable tool for functional studies, target gene identification, and the modeling of Multimerin-1 pathway restoration in tumor cells with silenced or reduced MMRN1 expression.

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