Calregulin Lentiviral Activation Particles (h): sc-400775-LAC

CALR encodes calregulin, an endoplasmic reticulum (ER) luminal chaperone that binds Ca²⁺ and coordinates glycoprotein folding and quality control through the calnexin/calreticulin cycle. Calregulin supports ER proteostasis by cooperating with ERp57 and lectin chaperone pathways to regulate disulfide bond formation, ER retention, and trafficking of nascent secretory and membrane proteins. Beyond the ER, calregulin influences Ca²⁺ homeostasis, integrin-dependent adhesion, and stress signaling linked to the unfolded protein response (UPR). Altered CALR activity and ER stress responses are associated with dysregulated immune signaling and oncogenic phenotypes, and CALR mutations have established relevance in myeloproliferative neoplasms, motivating mechanistic studies of protein folding and signaling consequences.

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

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