GPR40 Lentiviral Activation Particles (h2): sc-401434-LAC-2

Human FFAR1 (GPR40) encodes a G protein-coupled receptor for medium- and long-chain free fatty acids that couples primarily to Gαq/11 to drive phospholipase C activation, intracellular Ca2+ mobilization, and downstream PKC/MAPK signaling. In pancreatic β cells and other metabolically active tissues, GPR40 functions as a nutrient sensor linking lipid availability to regulated secretory responses and broader control of glucose–lipid homeostasis. Altered FFAR1 signaling has been implicated in metabolic dysregulation, including obesity-associated insulin secretory defects and type 2 diabetes-relevant phenotypes, and has also been explored in contexts such as inflammation and cancer metabolism. Gene editing of FFAR1 enables mechanistic dissection of fatty-acid–GPCR signaling, interrogation of β-cell stimulus–secretion coupling, and pathway mapping in cellular models using transcriptomic, phosphoproteomic, and functional assays.

GPR40 Lentiviral Activation Particles (h2) address this need by packaging the complete synergistic activation mediator (SAM) transcriptional activation system into transduction-ready, high-titer lentiviral particles, enabling efficient FFAR1 upregulation across a broader range of human cell types.

GPR40 Lentiviral Activation Particles (h2) 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 FFAR1 transcriptional start site, where VP64, p65, and HSF1 act cooperatively to recruit endogenous transcriptional machinery and drive sustained upregulation of endogenous GPR40 expression. The use of nuclease-inactive dCas9 avoids the introduction of double-strand DNA breaks and preserves the native FFAR1 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.