Plasma kallikrein B1 mRNA (KLKB1 mRNA) (KLKB1 mRNA)

Plasma kallikrein mRNA is the messenger RNA transcript of the KLKB1 gene, which encodes the precursor protein prekallikrein (UniProt P03952). Once translated and secreted primarily by the liver, prekallikrein is converted into the active serine protease plasma kallikrein, a central component of the kallikrein-kinin system (Kaplan & Ghebrehiwet, 2010). Plasma kallikrein plays a critical role in the inflammatory response by cleaving high-molecular-weight kininogen to release bradykinin, a potent mediator of vascular permeability and pain (Zuraw, 2008). In conditions like hereditary angioedema (HAE), deficiency in C1 esterase inhibitor leads to unregulated kallikrein activity and excessive bradykinin production, resulting in debilitating and potentially life-threatening swelling episodes (Maurer et al., 2022). Therapeutic targeting of the mRNA using antisense oligonucleotides (ASOs) like donidalorsen allows for the specific degradation of the transcript via RNase H1-mediated cleavage. This reduction in mRNA levels leads to a significant decrease in the hepatic production of prekallikrein, thereby lowering systemic kallikrein activity and preventing the biochemical cascade that leads to HAE attacks (Fereidouni et al., 2022). This approach represents a novel prophylactic strategy that offers long-lasting suppression of the disease pathway compared to traditional protein-based inhibitors.

Other names

Prekallikrein mRNAKLKB1 transcriptFletcher factor mRNA

Antisense oligonucleotide-mediated degradation of mRNA via RNase H1, resulting in reduced translation of prekallikrein protein (Cohn et al., 2020).