Plasma prekallikrein (KLKB1) mRNA (KLKB1 mRNA)

Plasma prekallikrein mRNA is the transcript of the KLKB1 gene, which encodes the zymogen precursor of plasma kallikrein (UniProt P03952). In the contact activation system, prekallikrein is converted to active kallikrein, which then cleaves high-molecular-weight kininogen to release bradykinin, a potent mediator of vascular permeability and inflammation (PubMed: 33053278). Overproduction of bradykinin due to dysregulated kallikrein activity is the primary driver of swelling in hereditary angioedema (HAE) (NIH: StatPearls). By targeting the mRNA transcript with antisense oligonucleotides like donidalorsen, the production of the prekallikrein protein can be significantly reduced at the source (NEJM: 385:11). This approach provides a prophylactic strategy to prevent the painful and potentially life-threatening edema attacks associated with HAE. Clinical trials have demonstrated that reducing prekallikrein levels via mRNA targeting effectively lowers the frequency of HAE attacks with a favorable safety profile (PubMed: 34551227).

Other names

Fletcher factor mRNAPlasma kallikrein B1 mRNAKLKB1 transcriptPrekallikrein messenger RNA

Antisense oligonucleotide-mediated degradation of mRNA via RNase H1 to inhibit the synthesis of plasma prekallikrein protein.