TLR3 Lentiviral Activation Particles (h2): sc-400512-LAC-2

Human TLR3 (Toll-like receptor 3) encodes an endosomal pattern-recognition receptor that detects viral double-stranded RNA and the synthetic analog poly(I:C), initiating innate immune signaling through the TRIF adaptor to activate IRF3/IRF7 and NF-κB and induce type I interferons and pro-inflammatory cytokines. TLR3 activity interfaces with antiviral restriction programs, dendritic cell maturation, and inflammatory transcriptional networks, and can modulate cell death pathways under certain stress contexts. Genetic variation or dysregulated TLR3 signaling has been linked to altered susceptibility to viral infections and to immune-mediated inflammatory phenotypes, making it relevant to studies of host–pathogen interactions, interferon biology, and neuroinflammation. Gene editing of TLR3 supports mechanistic dissection of endosomal nucleic acid sensing, pathway crosstalk with RIG-I/MDA5 signaling, and functional genomics screens in immune and epithelial models.

TLR3 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 TLR3 upregulation across a broader range of human cell types.

TLR3 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 TLR3 transcriptional start site, where VP64, p65, and HSF1 act cooperatively to recruit endogenous transcriptional machinery and drive sustained upregulation of endogenous TLR3 expression. The use of nuclease-inactive dCas9 avoids the introduction of double-strand DNA breaks and preserves the native TLR3 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.