ACVR2A & ACVR2B Knockout HEK293 Cell Line

ACVR2A and ACVR2B are the two type II activin receptors — serine/threonine kinase receptors that bind activins, myostatin (GDF8), GDF11, BMPs, and other TGF-β superfamily ligands; upon ligand binding, the type II receptor recruits and phosphorylates type I receptors (ALK4/ACVR1B, ALK5, ALK7), which then phosphorylate SMAD2/3 (activin/myostatin branch) to regulate gene expression. ACVR2A and ACVR2B share substantial ligand and functional overlap, with myostatin/GDF11-mediated muscle growth suppression being a major shared function. This ligand-trap axis is the basis of several clinically important therapeutics. This ACVR2A & ACVR2B Double Knockout in HEK293 is the gold-standard genetic tool for asking whether type II activin receptors are required for these processes — combined loss of ACVR2A and ACVR2B eliminates virtually all activin/myostatin/GDF11 type II receptor signaling, generating cells unable to transduce these TGF-β superfamily signals. Single-isoform rescue (ACVR2A alone or ACVR2B alone) in the double knockout enables paralog-specific functional dissection — the gold-standard experimental design for this receptor pair. For systematic activin/myostatin research, the EDITGENE ACVR2A & ACVR2B Double Knockout in HEK293 is uniquely valuable — single knockouts retain residual signaling from the other paralog; double knockout completely abolishes type II activin receptor function. This product complements the parallel single ACVR2A Knockouts in HEK293 and HAP1 (both also available). The double knockout is a critical specificity tool for ⭐⭐ sotatercept (Winrevair, FDA-approved 2024 for pulmonary arterial hypertension — a landmark PAH therapy), luspatercept (Reblozyl, for anemia), bimagrumab (anti-ActRII antibody for muscle wasting and obesity/metabolic disease), ramatercept, and the entire activin/myostatin ligand-trap therapeutic class — these traps act on both ACVR2A and ACVR2B, making the double knockout the definitive specificity control.

Primary applications: • Complete type II activin receptor elimination: activin/myostatin/GDF11-induced phospho-SMAD2/3 analysis — abolished in the double KO. • Single-isoform rescue: ⭐ re-introduction of ACVR2A alone or ACVR2B alone enables paralog-specific dissection — gold-standard experimental design. • Ligand trap specificity: critical genetic control for ⭐⭐ sotatercept (Winrevair, FDA-approved 2024 PAH), luspatercept (Reblozyl), bimagrumab, ramatercept — these traps act on both receptors, making the double KO the definitive specificity control. • Muscle/anemia/PAH biology: in heterologous disease-relevant contexts, complete activin/myostatin pathway loss phenotypes. EDITGENE recommends this double knockout as the gold-standard genetic tool for the activin/myostatin ligand-trap therapeutic field — one of the most clinically active TGF-β superfamily drug classes.

Yes, and rescue experiments are uniquely powerful in this double knockout: • Single-isoform rescue: ⭐ re-introduction of ACVR2A alone or ACVR2B alone in the double knockout enables paralog-specific functional dissection — gold-standard experimental design for the type II activin receptor pair. • Construct design: use codon-modified ACVR2A or ACVR2B sequences with small intracellular C-terminal tags (FLAG, HA) — preserve extracellular ligand-binding domain, transmembrane span, and kinase domain. • Kinase-dead rescue: K219R (ACVR2A) or K217R (ACVR2B) ATP-binding lysine mutations abolish catalytic activity. • Ligand-binding-deficient rescue: extracellular domain mutations enable separation of ligand-trapping from signaling. • Functional readout: rescue should restore activin/myostatin/GDF11-induced phospho-SMAD2/3; paralog-specific rescue reveals ACVR2A vs ACVR2B distinct contributions. HEK293 transduces efficiently with lentivirus and supports systematic isoform-specific rescue experiments for activin/myostatin ligand-trap research.