MSH2 Lentiviral Activation Particles (h): sc-400966-LAC

MSH2 encodes a core DNA mismatch repair (MMR) factor that heterodimerizes with MSH6 (MutSα) or MSH3 (MutSβ) to recognize base–base mismatches and insertion/deletion loops arising during replication. Following lesion recognition, MSH2-containing complexes coordinate downstream repair events with MLH1/PMS2 and replication-associated factors to preserve genome stability and limit mutagenesis. Disruption of MSH2-dependent MMR promotes microsatellite instability and elevated mutation burden, linking MSH2 dysfunction to hereditary and sporadic tumor biology. MSH2 is also implicated in cellular responses to certain DNA-damaging agents and replication stress, making it a useful node for studying DNA repair pathway crosstalk.

MSH2 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 MSH2 upregulation across a broader range of human cell types.

MSH2 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 MSH2 transcriptional start site, where VP64, p65, and HSF1 act cooperatively to recruit endogenous transcriptional machinery and drive sustained upregulation of endogenous MSH2 expression. The use of nuclease-inactive dCas9 avoids the introduction of double-strand DNA breaks and preserves the native MSH2 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.