Cryopyrin/NALP3/NLRP3 Lentiviral Activation Particles (m): sc-432122-LAC

Mouse Nlrp3 encodes cryopyrin (NALP3/NLRP3), a cytosolic pattern-recognition receptor that serves as a central sensor for diverse danger signals and sterile stress. Upon activation, NLRP3 nucleates inflammasome assembly with ASC and pro-caspase-1, driving caspase-1 activation, maturation of IL-1β and IL-18, and pyroptotic cell death through gasdermin D. This pathway links ionic flux, mitochondrial dysfunction, lysosomal rupture, and reactive oxygen species to innate immune signaling and downstream cytokine programs. Dysregulated NLRP3 activity is widely used as a mechanistic entry point for studying inflammatory pathology, including autoinflammatory phenotypes, metabolic inflammation, neuroinflammation, and host responses to infection in murine models.

Cryopyrin/NALP3/NLRP3 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 Nlrp3 upregulation across a broader range of human cell types.

Cryopyrin/NALP3/NLRP3 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 Nlrp3 transcriptional start site, where VP64, p65, and HSF1 act cooperatively to recruit endogenous transcriptional machinery and drive sustained upregulation of endogenous Cryopyrin/NALP3/NLRP3 expression. The use of nuclease-inactive dCas9 avoids the introduction of double-strand DNA breaks and preserves the native Nlrp3 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.