Klotho Lentiviral Activation Particles (h): sc-400970-LAC

Human KL encodes Klotho, a type I single-pass membrane protein that also exists as a soluble ectodomain, functioning as a key modulator of fibroblast growth factor signaling and systemic mineral metabolism. As an obligate co-receptor for FGF23, Klotho influences phosphate and vitamin D homeostasis and shapes downstream MAPK/ERK and PI3K/AKT pathway outputs in responsive tissues. Klotho has additionally been linked to regulation of oxidative stress responses, Wnt signaling, and cellular senescence programs that impact tissue remodeling and metabolic homeostasis. Altered KL expression has been associated with phenotypes relevant to kidney dysfunction, vascular calcification, and age-related cardiometabolic and neurodegenerative processes, supporting its use as a mechanistic node in pathway-focused research models.

Klotho 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 KL upregulation across a broader range of human cell types.

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