GGPS1 CRISPR Activation Plasmid (h): sc-404003-ACT

Human GGPS1 encodes geranylgeranyl diphosphate synthase 1, a key enzyme in the mevalonate pathway that produces geranylgeranyl pyrophosphate (GGPP) for protein prenylation and downstream isoprenoid biosynthesis. By supplying GGPP, GGPS1 supports membrane localization and signaling of small GTPases and other prenylated proteins, influencing vesicular trafficking, cytoskeletal dynamics, mitochondrial function, and broader metabolic homeostasis. Perturbation of GGPS1-linked prenylation has been associated with dysregulated growth and stress-response signaling and is frequently studied in contexts where mevalonate flux and prenylation-dependent pathways contribute to disease-relevant phenotypes. As a result, GGPS1 serves as a useful node for investigating lipid metabolism–signaling crosstalk, proteostasis, and pathway vulnerabilities in cellular models.

GGPS1 CRISPR Activation Plasmid (h) provides a targeted, non-destructive approach to upregulating endogenous GGPS1 expression without altering the underlying DNA sequence.

GGPS1 CRISPR Activation Plasmid (h) is a three-plasmid synergistic activation mediator (SAM) system engineered for highly efficient, site-specific transcriptional upregulation of the GGPS1 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 GGPS1 transcriptional start site, where VP64, p65, and HSF1 act in concert to recruit transcriptional machinery and drive upregulation of endogenous GGPS1 expression. Unlike nuclease-active Cas9, dCas9 does not introduce double-strand breaks or modify the genomic sequence, preserving the native GGPS1 locus and enabling the study of GGPS1-dependent transcriptional responses at the endogenous locus, making it a valuable tool for functional studies, target gene identification, and the modeling of GGPS1 pathway restoration in tumor cells with silenced or reduced GGPS1 expression.

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