Plasma kallikrein B1 (KLKB1) gene (KLKB1)

The KLKB1 gene, located on chromosome 4, encodes plasma prekallikrein, a zymogen synthesized primarily in the liver and secreted into the blood (NCBI Gene, 2024). Upon activation to plasma kallikrein, it plays a critical role in the kallikrein-kinin system by cleaving high-molecular-weight kininogen to release bradykinin, a potent mediator of vascular permeability (UniProt, 2024). In patients with hereditary angioedema (HAE), uncontrolled kallikrein activity leads to excessive bradykinin production, resulting in recurrent, painful, and potentially life-threatening swelling (Longhurst et al., NEJM, 2024). Targeting the KLKB1 genomic DNA within hepatocyte nuclei using CRISPR/Cas9 technology, such as with the investigational therapy NTLA-2002, aims to permanently knock out the gene (Intellia Therapeutics, 2024). This approach reduces the production of plasma prekallikrein at the source, thereby preventing the formation of bradykinin and reducing HAE attacks. Clinical data suggests that a single administration can lead to sustained reductions in plasma kallikrein levels and significant improvement in disease symptoms (Longhurst et al., NEJM, 2024).

Other names

Plasma prekallikrein geneFletcher factor geneKininogenin genePKK genePPK gene

CRISPR/Cas9-mediated gene knockout