ACSL4 Lentiviral Activation Particles (m2): sc-424503-LAC-2

Mouse Acsl4 encodes acyl-CoA synthetase long-chain family member 4 (ACSL4), a lipid-metabolizing enzyme that activates polyunsaturated long-chain fatty acids such as arachidonic acid to acyl-CoAs, shaping membrane phospholipid composition and downstream eicosanoid biosynthesis. ACSL4 functions at the intersection of fatty acid uptake, phospholipid remodeling, and redox homeostasis, and is widely used as a molecular determinant of ferroptosis sensitivity through its role in generating oxidizable PUFA-containing phospholipids. Altered ACSL4 activity has been linked to dysregulated lipid signaling and oxidative stress responses in models of neurodegeneration, metabolic dysfunction, inflammation, and cancer-relevant pathways. Acsl4-targeted gene editing enables mechanistic studies of lipid flux, ferroptotic cell death, and membrane remodeling across cell types and in vivo mouse systems.

ACSL4 Lentiviral Activation Particles (m2) address this need by packaging the complete synergistic activation mediator (SAM) transcriptional activation system into transduction-ready, high-titer lentiviral particles, enabling efficient Acsl4 upregulation across a broader range of human cell types.

ACSL4 Lentiviral Activation Particles (m2) 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 Acsl4 transcriptional start site, where VP64, p65, and HSF1 act cooperatively to recruit endogenous transcriptional machinery and drive sustained upregulation of endogenous ACSL4 expression. The use of nuclease-inactive dCas9 avoids the introduction of double-strand DNA breaks and preserves the native Acsl4 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.