GFRαL Lentiviral Activation Particles (h): sc-415831-LAC

Human GFRAL (GDNF family receptor alpha-like) encodes a glycosylphosphatidylinositol-anchored co-receptor that confers ligand specificity to RET signaling in response to the stress cytokine GDF15. GFRAL is enriched in hindbrain neuronal populations that integrate metabolic and visceral cues, linking extracellular GDF15 to intracellular RET-driven cascades such as MAPK/ERK and PI3K/AKT that influence neuronal activity and energy balance. Through this axis, GFRAL is widely studied in pathways governing appetite regulation, nausea/aversive responses, and systemic metabolic adaptation to inflammation or mitochondrial stress. Dysregulation of the GDF15–GFRAL–RET pathway is associated with altered body weight control and metabolic phenotypes, motivating mechanistic research in obesity, cachexia, and related neuro-metabolic contexts.

GFRαL 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 GFRAL upregulation across a broader range of human cell types.

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