SHIP-1 Lentiviral Activation Particles (m): sc-421137-LAC

Inpp5d encodes SHIP-1 (SH2 domain-containing inositol 5-phosphatase 1), a hematopoietic-enriched negative regulator of phosphoinositide signaling that hydrolyzes PI(3,4,5)P3 to PI(3,4)P2 and attenuates PI3K–AKT pathway output. In mouse immune lineages, SHIP-1 helps tune signaling downstream of receptors such as Fc receptors, cytokine receptors, and BCR/TLR pathways, shaping myeloid and lymphoid activation thresholds. Through crosstalk with MAPK signaling, apoptosis regulators, and cytoskeletal programs, it influences proliferation, survival, migration, and inflammatory mediator production. Dysregulated Inpp5d/SHIP-1 activity is widely studied in immune dysfunction and inflammation-associated phenotypes, making it relevant for mechanistic work in macrophage, microglial, B cell, and mast cell models.

SHIP-1 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 Inpp5d upregulation across a broader range of human cell types.

SHIP-1 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 Inpp5d transcriptional start site, where VP64, p65, and HSF1 act cooperatively to recruit endogenous transcriptional machinery and drive sustained upregulation of endogenous SHIP-1 expression. The use of nuclease-inactive dCas9 avoids the introduction of double-strand DNA breaks and preserves the native Inpp5d 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.