Plasma protease C1 inhibitor (C1-INH) (C1-INH)

The SERPING1 gene encodes the Plasma protease C1 inhibitor (C1-INH), a critical serine protease inhibitor (serpin) that regulates the complement, contact (kallikrein-kinin), and coagulation systems [1, 2]. Its primary function is to inhibit C1r and C1s in the classical complement pathway, as well as plasma kallikrein and factor XIIa in the contact system, thereby preventing the excessive generation of bradykinin [1, 3]. Mutations in the SERPING1 gene lead to Hereditary Angioedema (HAE), a condition characterized by recurrent, life-threatening episodes of subcutaneous and submucosal swelling [3, 5]. The therapeutic approach involving the SERPING1 gene in autologous hematopoietic stem cells (HSCs) involves the ex vivo genetic modification of a patient's own stem cells to express a functional version of the gene [4]. Once re-infused, these modified HSCs engraft in the bone marrow and provide a continuous, endogenous supply of functional C1-INH, potentially offering a long-term or curative solution for HAE patients by restoring physiological regulation of inflammatory cascades [4, 6].

Other names

SERPING1C1 esterase inhibitorSerpin family G member 1C1InhHAE1HAE2

The primary mechanism of action is the inhibition of serine proteases, specifically C1r, C1s, plasma kallikrein, and coagulation factor XIIa, which regulates the activation of the complement and contact systems [1, 3]. In the context of autologous hematopoietic stem cell gene therapy, the mechanism involves the ex vivo introduction of a functional SERPING1 gene into the patient's stem cells, which then engraft and provide a continuous endogenous source of functional C1-INH protein to prevent bradykinin-mediated angioedema [4, 6].