P-KLKB1-101

P-KLKB1-101 is an investigational, fully non-viral gene-editing therapy developed by Poseida Therapeutics for the treatment of hereditary angioedema (HAE). It uses the Cas-CLOVER site-specific gene editing system to target and inactivate the *KLKB1* gene in liver cells, which encodes prekallikrein—a precursor of kallikrein. By disrupting *KLKB1*, P-KLKB1-101 reduces kallikrein protein levels and activity, thereby lowering bradykinin production and preventing HAE swelling attacks. The therapy has demonstrated high-fidelity editing with minimal off-target effects (≤0.1%) in preclinical studies involving human hepatocytes, mice, and non-human primates. The reduction in kallikrein was dose-dependent and sustained for at least six months post-treatment. As a non-viral approach, it offers potential advantages such as repeat dosing if needed and reduced risk of immune response compared to viral vector-based therapies[2][5][7].