FXR/NR1H4 Lentiviral Activation Particles (h): sc-417410-LAC

NR1H4 encodes the farnesoid X receptor (FXR), a ligand-activated nuclear receptor that functions as a transcriptional regulator of bile acid, cholesterol, and lipid homeostasis. FXR integrates signals from bile acids to control gene networks governing bile acid synthesis and transport, including feedback regulation of hepatic metabolic pathways and enterohepatic cycling. Through crosstalk with nuclear receptor and inflammatory signaling programs, FXR influences hepatocyte and enterocyte physiology, barrier function, and metabolic adaptation. Dysregulation of NR1H4/FXR activity has been associated with cholestatic and metabolic liver phenotypes and is frequently studied in the context of steatosis, nonalcoholic fatty liver disease, and gut–liver axis dysfunction.

FXR/NR1H4 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 NR1H4 upregulation across a broader range of human cell types.

FXR/NR1H4 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 NR1H4 transcriptional start site, where VP64, p65, and HSF1 act cooperatively to recruit endogenous transcriptional machinery and drive sustained upregulation of endogenous FXR/NR1H4 expression. The use of nuclease-inactive dCas9 avoids the introduction of double-strand DNA breaks and preserves the native NR1H4 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.