CIS Lentiviral Activation Particles (m): sc-419665-LAC

Mouse Cish encodes cytokine-inducible SH2-containing protein (CIS), a SOCS family adaptor that acts as a feedback inhibitor of cytokine receptor signaling. CIS binds phosphorylated receptor motifs and associated JAK kinases to dampen downstream STAT phosphorylation, thereby shaping signaling outputs from pathways such as IL-2/IL-7 and related γc cytokine responses. Through regulation of cytokine sensitivity, CIS influences immune cell activation, proliferation, and differentiation programs, with research relevance to inflammation, autoimmunity, infection biology, and tumor immunology models. Altered Cish activity is therefore used to probe how negative regulation of JAK–STAT signaling impacts cell-state transitions and immune effector functions in vivo and in vitro.

CIS 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 Cish upregulation across a broader range of human cell types.

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