XBP1 Lentiviral Activation Particles (m): sc-423727-LAC

Xbp1 encodes XBP1, a basic leucine zipper transcription factor that is a central effector of the unfolded protein response during endoplasmic reticulum stress. Upon IRE1-mediated splicing, active XBP1 programs transcriptional networks that expand ER folding capacity, regulate ER-associated degradation, and remodel secretory pathway and lipid biosynthesis processes. In mouse systems, XBP1 activity shapes differentiation and function of highly secretory cell types and integrates metabolic and inflammatory signaling through ER stress pathways. Dysregulated XBP1 signaling is widely used as a mechanistic entry point to study proteostasis imbalance, immune cell adaptation, and stress-linked pathology models.

XBP1 Lentiviral Activation Particles (m) address this need by packaging the complete synergistic activation mediator (SAM) transcriptional activation system into transduction-ready, high-titer lentiviral particles, enabling efficient Xbp1 upregulation across a broader range of human cell types.

XBP1 Lentiviral Activation Particles (m) 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 Xbp1 transcriptional start site, where VP64, p65, and HSF1 act cooperatively to recruit endogenous transcriptional machinery and drive sustained upregulation of endogenous XBP1 expression. The use of nuclease-inactive dCas9 avoids the introduction of double-strand DNA breaks and preserves the native Xbp1 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.