PACE4 Lentiviral Activation Particles (h2): sc-405605-LAC-2

Human PCSK6 encodes the proprotein convertase PACE4, a calcium-dependent serine endoprotease that processes secreted and cell-surface precursor proteins at basic residue motifs to generate mature, bioactive factors. PACE4 contributes to post-translational activation of growth factors, metalloproteinases, receptors, and adhesion-related proteins, linking PCSK6 activity to extracellular matrix remodeling, cell migration, and developmental signaling networks including TGF-β/BMP-associated pathways. Dysregulated PCSK6 expression or activity has been associated with aberrant proteolytic processing in cancer biology, fibrosis-related tissue remodeling, and cardiovascular phenotypes, reflecting its role in regulating paracrine signaling and protease cascades. PCSK6/PACE4 perturbation is therefore used in gene editing and functional genomics studies to interrogate convertase-dependent substrate maturation, secretory pathway proteostasis, and downstream changes in invasion, differentiation, and inflammatory signaling outputs.

PACE4 Lentiviral Activation Particles (h2) address this need by packaging the complete synergistic activation mediator (SAM) transcriptional activation system into transduction-ready, high-titer lentiviral particles, enabling efficient PCSK6 upregulation across a broader range of human cell types.

PACE4 Lentiviral Activation Particles (h2) deliver all functional components of the synergistic activation mediator (SAM) system via lentiviral transduction. The system comprises three particle preparations co-transduced into target cells: one encoding catalytically inactive dCas9 (D10A and N863A mutations) fused to the VP64 transactivation domain with a blasticidin resistance gene; one encoding the MS2-p65-HSF1 fusion protein with a hygromycin resistance gene; and one encoding a target-specific 20 nt sgRNA fused to two MS2 RNA aptamers with a puromycin resistance gene. Following lentiviral transduction and genomic integration of the expression cassettes, the SAM components are stably expressed and assemble at the target locus within the proximal promoter region upstream of the PCSK6 transcriptional start site, where VP64, p65, and HSF1 act cooperatively to recruit endogenous transcriptional machinery and drive sustained upregulation of endogenous PACE4 expression. The use of nuclease-inactive dCas9 avoids the introduction of double-strand DNA breaks and preserves the native PCSK6 genomic locus and regulatory architecture.

The lentiviral format offers several practical advantages: stable genomic integration supports heritable activation across cell divisions; high-titer particle preparations eliminate the need for in-house viral production; and compatibility with primary, non-dividing, and transfection-resistant cell types expands experimental accessibility. Successful transduction can be confirmed and enriched through triple antibiotic selection using puromycin, hygromycin, and blasticidin.

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