TFEB Lentiviral Activation Particles (h): sc-401388-LAC

Transcription factor EB (TFEB) is a master regulator of lysosomal biogenesis and autophagy, coordinating expression of the CLEAR network to maintain proteostasis and cellular adaptation to nutrient and oxidative stress. TFEB activity is tightly controlled by nutrient-sensing pathways including mTORC1-dependent phosphorylation and cytoplasmic retention, with stress-induced nuclear translocation driving lysosome–autophagy gene programs. Through regulation of endolysosomal trafficking, lipid catabolism, and mitochondrial quality control, TFEB influences inflammatory signaling and metabolic homeostasis in diverse cell types. Dysregulated TFEB signaling has been implicated in lysosomal storage disorders, neurodegenerative disease models, cancer cell adaptation, and cardiometabolic dysfunction, making it a useful node for pathway interrogation in human systems.

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

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