Mannan-binding lectin serine protease 2 (MASP2) (MASP2)

Mannan-binding lectin serine protease 2 (MASP-2) is a key enzyme in the lectin pathway of the complement system, which is a vital part of the innate immune response [1, 2]. It is primarily produced in the liver and circulates as a zymogen associated with pattern recognition molecules such as mannan-binding lectin (MBL) and ficolins [1]. Upon recognition of pathogens or damaged tissue, MASP-2 is activated and cleaves complement components C4 and C2, leading to the formation of C3 convertase and subsequent inflammatory responses [5]. Overactivation of this pathway is linked to several conditions, including IgA nephropathy and hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA) [4, 5]. Therapeutic targeting of MASP2 mRNA using antisense oligonucleotides (ASOs) like IONIS-MASP2-LRx aims to reduce the systemic levels of the MASP-2 protein, thereby inhibiting the lectin pathway while preserving the classical and alternative complement pathways [3, 4]. This approach offers a targeted treatment for complement-mediated diseases with potentially fewer side effects than broad complement inhibition [4].

Other names

MASP-2Mannose-binding lectin-associated serine protease 2sMAPMAp19Mannan-binding lectin serine peptidase 2

Antisense oligonucleotide-mediated degradation of MASP2 mRNA to reduce protein synthesis and inhibit the lectin pathway of the complement system [3, 4].