Waf1/Cip1/CDKN1A p21 Lentiviral Activation Particles (h): sc-400013-LAC

CDKN1A encodes p21 (Waf1/Cip1), a cyclin-dependent kinase inhibitor that enforces cell-cycle checkpoints by inhibiting CDK2- and CDK1-containing complexes and coordinating G1/S and G2/M transitions. p21 is a prominent downstream effector of p53 signaling and integrates DNA damage responses, replication stress, and senescence programs through modulation of PCNA-dependent DNA synthesis and checkpoint control. By tuning proliferative arrest versus recovery, CDKN1A influences pathways linked to genomic stability, cellular differentiation, and apoptosis-adjacent stress adaptation. Dysregulated p21 expression or context-dependent function is implicated across cancer biology, therapy resistance models, fibrosis-associated senescence, and inflammatory microenvironment phenotypes studied in human cells.

Waf1/Cip1/CDKN1A p21 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 CDKN1A upregulation across a broader range of human cell types.

Waf1/Cip1/CDKN1A p21 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 CDKN1A transcriptional start site, where VP64, p65, and HSF1 act cooperatively to recruit endogenous transcriptional machinery and drive sustained upregulation of endogenous Waf1/Cip1/CDKN1A p21 expression. The use of nuclease-inactive dCas9 avoids the introduction of double-strand DNA breaks and preserves the native CDKN1A 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.