LRP4 CRISPR Activation Plasmid (h): sc-401708-ACT

LRP4 (low-density lipoprotein receptor-related protein 4) is a single-pass transmembrane receptor that functions as a key organizer of extracellular ligand signaling at the cell surface. In human tissues, LRP4 participates in Wnt and agrin-mediated signaling networks that regulate synapse organization, receptor clustering, and tissue patterning, supporting processes such as neuromuscular junction formation and skeletal homeostasis. Through interactions with secreted ligands and co-receptors, LRP4 influences downstream transcriptional programs that control cell–cell communication and developmental signaling. Dysregulated LRP4 expression or function has been linked to neuromuscular and bone-related phenotypes, making it a relevant target for mechanistic studies of synaptic signaling and musculoskeletal biology.

LRP4 CRISPR Activation Plasmid (h) provides a targeted, non-destructive approach to upregulating endogenous LRP4 expression without altering the underlying DNA sequence.

LRP4 CRISPR Activation Plasmid (h) is a three-plasmid synergistic activation mediator (SAM) system engineered for highly efficient, site-specific transcriptional upregulation of the LRP4 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 LRP4 transcriptional start site, where VP64, p65, and HSF1 act in concert to recruit transcriptional machinery and drive upregulation of endogenous LRP4 expression. Unlike nuclease-active Cas9, dCas9 does not introduce double-strand breaks or modify the genomic sequence, preserving the native LRP4 locus and enabling the study of LRP4-dependent transcriptional responses at the endogenous locus, making it a valuable tool for functional studies, target gene identification, and the modeling of LRP4 pathway restoration in tumor cells with silenced or reduced LRP4 expression.

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