Six2 Lentiviral Activation Particles (m): sc-422957-LAC

Six2 (sine oculis homeobox homolog 2) is a homeobox transcription factor that regulates progenitor cell maintenance and lineage decisions during mouse organogenesis, with prominent roles in nephron progenitor self-renewal and craniofacial and skeletal patterning. It acts within developmental transcriptional networks and integrates signaling inputs, including WNT/β-catenin, FGF, BMP, and Notch-associated programs, to control proliferation and differentiation timing. Dysregulated SIX2 activity is linked to aberrant developmental trajectories and has been associated with altered epithelial–mesenchymal states and proliferative programs relevant to congenital anomalies and tumor biology. In experimental systems, Six2 serves as a key node for dissecting gene regulatory circuits that govern stemness, morphogenesis, and tissue specification.

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

Six2 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 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.