SIRT3 Lentiviral Activation Particles (m): sc-425704-LAC

Mouse Sirt3 encodes the mitochondrial NAD+-dependent deacetylase SIRT3, a central regulator of protein acetylation status within the mitochondrial matrix. SIRT3 modulates oxidative phosphorylation, fatty acid β-oxidation, ketone body metabolism, and antioxidant defenses by deacetylating enzymes such as SOD2 and components of the electron transport chain, thereby influencing ATP production and reactive oxygen species homeostasis. Through links to AMPK–PGC-1α signaling, mitochondrial biogenesis, and stress responses, SIRT3 is widely studied in metabolic adaptation and aging-related mitochondrial dysfunction. Altered SIRT3 activity and mitochondrial protein hyperacetylation have been associated with neurodegeneration, cardiometabolic stress, and tumor biology in preclinical systems, supporting its use as a mechanistic node in mitochondrial disease-relevant pathways.

SIRT3 Lentiviral Activation Particles (m) address this need by packaging the complete synergistic activation mediator (SAM) transcriptional activation system into transduction-ready, high-titer lentiviral particles, enabling efficient Sirt3 upregulation across a broader range of human cell types.

SIRT3 Lentiviral Activation Particles (m) 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 Sirt3 transcriptional start site, where VP64, p65, and HSF1 act cooperatively to recruit endogenous transcriptional machinery and drive sustained upregulation of endogenous SIRT3 expression. The use of nuclease-inactive dCas9 avoids the introduction of double-strand DNA breaks and preserves the native Sirt3 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.