FKHR/FOXO1 Lentiviral Activation Particles (h): sc-400137-LAC

FOXO1 (FKHR) is a forkhead box transcription factor that integrates insulin/IGF-1 signaling with cellular programs controlling metabolism, oxidative stress responses, autophagy, and cell-cycle regulation. Its activity is tightly regulated by PI3K–AKT–mediated phosphorylation and nuclear-cytoplasmic shuttling, linking nutrient status to transcriptional control of gluconeogenic, apoptotic, and differentiation-associated genes. FOXO1 also interfaces with TGF-β, Wnt/β-catenin, and MAPK pathways to shape lineage decisions and stress adaptation. Dysregulated FOXO1 signaling has been implicated in metabolic dysfunction and oncogenic processes, including contexts where altered FOXO1 transcriptional outputs affect proliferation, survival, and immune cell homeostasis.

FKHR/FOXO1 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 FOXO1 upregulation across a broader range of human cell types.

FKHR/FOXO1 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 FOXO1 transcriptional start site, where VP64, p65, and HSF1 act cooperatively to recruit endogenous transcriptional machinery and drive sustained upregulation of endogenous FKHR/FOXO1 expression. The use of nuclease-inactive dCas9 avoids the introduction of double-strand DNA breaks and preserves the native FOXO1 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.