HEXB Lentiviral Activation Particles (h): sc-404765-LAC

Human HEXB encodes the beta subunit of lysosomal β-hexosaminidase, which partners with the alpha subunit to form Hex A and with itself to form Hex B, enabling stepwise degradation of GM2 ganglioside and related glycoconjugates. This lysosomal hydrolase activity supports glycosphingolipid catabolism, endo-lysosomal homeostasis, and turnover of membrane-derived substrates during autophagy and vesicular trafficking. Altered HEXB function perturbs ganglioside clearance and lysosomal substrate handling, making it a key node for studying mechanisms of lysosomal storage dysfunction and downstream effects on neuronal and glial biology. HEXB is therefore relevant to models that interrogate lipid metabolism, lysosome-centered stress responses, and pathways linking substrate accumulation to cellular dysfunction.

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

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