Notch1 Lentiviral Activation Particles (h): sc-400167-LAC

NOTCH1 encodes the transmembrane receptor Notch1, a central determinant of cell fate decisions during development and tissue homeostasis. Ligand engagement triggers proteolytic processing and release of the Notch intracellular domain, which translocates to the nucleus to regulate CSL/RBPJ-dependent transcriptional programs controlling proliferation, differentiation, and stem-like states. Notch1 signaling interfaces with pathways such as Wnt, TGF-β, NF-κB, and PI3K–AKT to shape context-specific transcriptional outputs and lineage commitment. Dysregulated NOTCH1 activity is implicated in oncogenic transformation and aberrant differentiation in multiple human disease settings, motivating mechanistic studies of pathway wiring and target gene networks.

Notch1 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 NOTCH1 upregulation across a broader range of human cell types.

Notch1 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 NOTCH1 transcriptional start site, where VP64, p65, and HSF1 act cooperatively to recruit endogenous transcriptional machinery and drive sustained upregulation of endogenous Notch1 expression. The use of nuclease-inactive dCas9 avoids the introduction of double-strand DNA breaks and preserves the native NOTCH1 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.