FUS/TLS Lentiviral Activation Particles (h): sc-400612-LAC

FUS (FUS/TLS) encodes an RNA/DNA-binding protein that couples transcriptional regulation with pre-mRNA splicing, mRNA transport, and stress granule dynamics. FUS participates in genome maintenance by coordinating DNA damage response and repair, including pathways linked to double-strand break signaling, and it influences RNA polymerase II–associated transcriptional programs. Through its low-complexity domains, FUS undergoes phase separation that shapes ribonucleoprotein assemblies and affects neuronal proteostasis. Dysregulation or mutation of FUS is strongly associated with neurodegenerative disease biology, particularly amyotrophic lateral sclerosis and frontotemporal dementia, and is also studied in contexts of genomic instability and sarcoma-associated fusion oncogenes.

FUS/TLS 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 FUS upregulation across a broader range of human cell types.

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