LRP1 CRISPR Activation Plasmid (h): sc-400638-ACT

LRP1 (low-density lipoprotein receptor–related protein 1) is a multifunctional endocytic and signaling receptor that binds diverse ligands, including apolipoprotein E–containing lipoproteins, α2-macroglobulin–protease complexes, and extracellular matrix–associated factors. It regulates receptor-mediated uptake and trafficking, controls extracellular protease clearance, and coordinates signaling through pathways such as MAPK/ERK, PI3K/AKT, and TGF-β in a cell type–dependent manner. Human LRP1 influences lipid handling, cell migration, and vascular homeostasis, and has been implicated in neurobiology through roles in amyloid-β transport and synaptic regulation. Altered LRP1 expression or function is associated with cardiometabolic traits, atherosclerosis-related processes, and neurodegenerative and cancer-relevant mechanisms involving extracellular matrix remodeling and growth factor signaling.

LRP1 CRISPR Activation Plasmid (h) provides a targeted, non-destructive approach to upregulating endogenous LRP1 expression without altering the underlying DNA sequence.

LRP1 CRISPR Activation Plasmid (h) is a three-plasmid synergistic activation mediator (SAM) system engineered for highly efficient, site-specific transcriptional upregulation of the LRP1 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 LRP1 transcriptional start site, where VP64, p65, and HSF1 act in concert to recruit transcriptional machinery and drive upregulation of endogenous LRP1 expression. Unlike nuclease-active Cas9, dCas9 does not introduce double-strand breaks or modify the genomic sequence, preserving the native LRP1 locus and enabling the study of LRP1-dependent transcriptional responses at the endogenous locus, making it a valuable tool for functional studies, target gene identification, and the modeling of LRP1 pathway restoration in tumor cells with silenced or reduced LRP1 expression.

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