Pdcd-1 Lentiviral Activation Particles (h2): sc-403008-LAC-2

Human PDCD1 encodes the inhibitory immune checkpoint receptor PD-1 (Pdcd-1), a type I membrane protein expressed on activated T cells, B cells, and subsets of myeloid cells that constrains antigen receptor signaling to maintain peripheral tolerance. Upon engagement by PD-L1 or PD-L2, PD-1 recruits SHP2 phosphatase via its ITIM/ITSM motifs to dampen proximal TCR/CD28 signaling, limiting PI3K–AKT and RAS–MAPK pathway activity and reshaping transcriptional programs linked to effector function, metabolism, and exhaustion. Dysregulated PDCD1 expression or signaling is associated with chronic infection and tumor-associated immune dysfunction as well as autoimmunity, reflecting its central role in balancing immune activation and suppression. PDCD1-targeted gene editing and perturbation studies enable mechanistic dissection of checkpoint signaling, immune cell fate decisions, and ligand-dependent inhibitory networks in primary human lymphocytes and engineered in vitro models.

Pdcd-1 Lentiviral Activation Particles (h2) address this need by packaging the complete synergistic activation mediator (SAM) transcriptional activation system into transduction-ready, high-titer lentiviral particles, enabling efficient PDCD1 upregulation across a broader range of human cell types.

Pdcd-1 Lentiviral Activation Particles (h2) 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 PDCD1 transcriptional start site, where VP64, p65, and HSF1 act cooperatively to recruit endogenous transcriptional machinery and drive sustained upregulation of endogenous Pdcd-1 expression. The use of nuclease-inactive dCas9 avoids the introduction of double-strand DNA breaks and preserves the native PDCD1 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.