Six2 Lentiviral Activation Particles (h): sc-402975-LAC

SIX2 encodes Six2, a homeobox transcription factor that regulates progenitor cell maintenance and lineage specification during human kidney and craniofacial development. Six2 functions in transcriptional networks controlling nephron progenitor self-renewal and differentiation, integrating with pathways such as WNT/β-catenin, FGF, and BMP signaling to balance growth and maturation programs. Dysregulated SIX2 expression has been associated with developmental disorders affecting renal morphogenesis and craniofacial patterning, and altered SIX2 activity is also studied in contexts of epithelial–mesenchymal plasticity and tumor biology. As a nuclear DNA-binding regulator, Six2 provides a tractable node for dissecting gene regulatory circuits that govern differentiation state and tissue identity.

Six2 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 SIX2 upregulation across a broader range of human cell types.

Six2 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 SIX2 transcriptional start site, where VP64, p65, and HSF1 act cooperatively to recruit endogenous transcriptional machinery and drive sustained upregulation of endogenous Six2 expression. The use of nuclease-inactive dCas9 avoids the introduction of double-strand DNA breaks and preserves the native SIX2 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.