RANK Lentiviral Activation Particles (h): sc-400559-LAC

Human TNFRSF11A encodes RANK (receptor activator of NF-κB), a TNF receptor superfamily member that transduces RANKL-dependent signals to regulate osteoclast differentiation, survival, and bone remodeling. RANK engagement activates canonical and non-canonical NF-κB signaling and intersects with MAPK and PI3K/AKT pathways to coordinate transcriptional programs controlling immune cell communication and tissue homeostasis. Dysregulated RANK pathway activity has been associated with disorders of bone turnover and inflammatory microenvironments, and it is frequently studied in contexts linking skeletal biology with immune signaling. As a membrane receptor with well-defined ligand–receptor dynamics, RANK provides a tractable entry point for mechanistic studies of osteoimmunology and NF-κB–driven gene networks.

RANK 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 TNFRSF11A upregulation across a broader range of human cell types.

RANK 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 TNFRSF11A transcriptional start site, where VP64, p65, and HSF1 act cooperatively to recruit endogenous transcriptional machinery and drive sustained upregulation of endogenous RANK expression. The use of nuclease-inactive dCas9 avoids the introduction of double-strand DNA breaks and preserves the native TNFRSF11A 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.