NEDD8 Lentiviral Activation Particles (h): sc-417924-LAC

NEDD8 encodes neural precursor cell expressed developmentally downregulated protein 8, a ubiquitin-like modifier that is conjugated to targets through the neddylation cascade (E1 NAE1/UBA3, E2 UBE2M/UBE2F, and E3 ligases). NEDD8 conjugation is a central regulator of cullin-RING ubiquitin ligases, promoting ubiquitin-dependent turnover of proteins that control cell-cycle progression, DNA replication, stress responses, and signal transduction. By tuning proteostasis and checkpoint control, NEDD8 influences pathways linked to genome stability and inflammatory signaling. Dysregulated neddylation has been associated with altered proliferation programs and aberrant protein degradation networks observed across multiple disease-relevant cellular states.

NEDD8 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 NEDD8 upregulation across a broader range of human cell types.

NEDD8 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 NEDD8 transcriptional start site, where VP64, p65, and HSF1 act cooperatively to recruit endogenous transcriptional machinery and drive sustained upregulation of endogenous NEDD8 expression. The use of nuclease-inactive dCas9 avoids the introduction of double-strand DNA breaks and preserves the native NEDD8 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.