NPAS4 Lentiviral Activation Particles (h): sc-402373-LAC

NPAS4 (neuronal PAS domain protein 4) is an activity-dependent basic helix–loop–helix PAS transcription factor that couples calcium signaling to rapid transcriptional programs in neurons. It regulates excitation–inhibition balance by controlling gene networks involved in synapse formation, inhibitory synaptic scaling, and neurotrophin signaling, including pathways linked to BDNF-responsive transcription. NPAS4 is implicated in neuronal plasticity, learning and memory, and stress-responsive circuitry, and altered NPAS4 regulation has been associated with neuropsychiatric and neurodegenerative disease-relevant phenotypes. As a context-sensitive transcriptional regulator, it is widely used to interrogate stimulus-driven gene expression and circuit-level adaptations in human neuronal models.

NPAS4 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 NPAS4 upregulation across a broader range of human cell types.

NPAS4 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 NPAS4 transcriptional start site, where VP64, p65, and HSF1 act cooperatively to recruit endogenous transcriptional machinery and drive sustained upregulation of endogenous NPAS4 expression. The use of nuclease-inactive dCas9 avoids the introduction of double-strand DNA breaks and preserves the native NPAS4 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.