Waf1/Cip1/CDKN1A p21 Lentiviral Activation Particles (m): sc-419607-LAC

Mouse Cdkn1a encodes the cyclin-dependent kinase inhibitor p21 (Waf1/Cip1), a key effector of p53-dependent stress responses that restrains CDK2- and CDK4/6-driven cell-cycle progression at the G1/S checkpoint. By directly modulating cyclin–CDK activity and proliferating cell nuclear antigen (PCNA)-associated DNA replication and repair processes, p21 integrates signals from DNA damage, oxidative stress, and oncogene activation to coordinate cell-cycle arrest, senescence, and context-dependent apoptosis. Cdkn1a is therefore central to pathways governing genome stability and tissue homeostasis, and its dysregulation is widely used as a molecular readout in studies of tumor suppressor signaling, inflammation-associated tissue remodeling, and aging-related cellular senescence in mouse models.

Waf1/Cip1/CDKN1A p21 Lentiviral Activation Particles (m) 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 (m) 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.