ACTR-IIB CRISPR Activation Plasmid (h): sc-401414-ACT

ACVR2B encodes activin receptor type IIB (ACTR-IIB), a transmembrane serine/threonine kinase receptor in the TGF-β superfamily that binds ligands such as activins, myostatin (GDF8), and GDF11. Ligand engagement promotes assembly with type I receptors and phosphorylation of SMAD2/3, coordinating transcriptional programs that regulate cellular growth, differentiation, extracellular matrix remodeling, and endocrine signaling. ACTR-IIB-dependent signaling contributes to tissue homeostasis in muscle, reproductive and metabolic biology, and immune modulation through context-specific crosstalk with MAPK and PI3K/AKT pathways. Dysregulated ACVR2B activity has been associated with altered muscle mass phenotypes and broader perturbations in TGF-β/activin pathway signaling implicated in fibrosis, inflammation, and tumor-associated microenvironment remodeling.

ACTR-IIB CRISPR Activation Plasmid (h) provides a targeted, non-destructive approach to upregulating endogenous ACVR2B expression without altering the underlying DNA sequence.

ACTR-IIB CRISPR Activation Plasmid (h) is a three-plasmid synergistic activation mediator (SAM) system engineered for highly efficient, site-specific transcriptional upregulation of the ACVR2B locus in human cell lines. The system is built around a catalytically inactive Cas9 (dCas9) carrying two inactivating mutations (D10A and N863A) that eliminate nuclease activity while preserving DNA binding. This dCas9 is fused to VP64, a potent transcriptional activator, and is co-expressed with a blasticidin resistance gene for selection. The second plasmid encodes the MS2-p65-HSF1 fusion protein, a secondary activator complex that works in concert with dCas9-VP64, alongside a hygromycin resistance gene. The third plasmid encodes a target-specific 20 nt sgRNA fused to two MS2 RNA aptamers that recruit the MS2-p65-HSF1 complex to the activation site, accompanied by a puromycin resistance gene. The three plasmids are delivered at a 1:1:1 mass ratio for balanced expression of all system components.

Once assembled at the target locus, the SAM complex binds within approximately 200 bp upstream of the ACVR2B transcriptional start site, where VP64, p65, and HSF1 act in concert to recruit transcriptional machinery and drive upregulation of endogenous ACTR-IIB expression. Unlike nuclease-active Cas9, dCas9 does not introduce double-strand breaks or modify the genomic sequence, preserving the native ACVR2B locus and enabling the study of ACTR-IIB-dependent transcriptional responses at the endogenous locus, making it a valuable tool for functional studies, target gene identification, and the modeling of ACTR-IIB pathway restoration in tumor cells with silenced or reduced ACVR2B expression.

For Research Use Only. Not Intended for Diagnostic or Therapeutic Use.