Plasma kallikrein B1 (KLKB1) (KLKB1)

The Plasma kallikrein B1 (KLKB1) genomic DNA locus, located on chromosome 4q35, encodes the plasma prekallikrein protein, which is primarily synthesized and secreted by hepatocytes (Source: NCBI Gene ID 3818). Plasma prekallikrein is a zymogen that, upon activation to plasma kallikrein, plays a critical role in the kinin-kallikrein system by cleaving high-molecular-weight kininogen to release bradykinin (Source: UniProt P03952). Bradykinin is a potent inflammatory mediator that increases vascular permeability; its unregulated production is the primary cause of the debilitating and potentially life-threatening swelling episodes characteristic of hereditary angioedema (HAE) (Source: StatPearls, Hereditary Angioedema). The KLKB1 gene is the specific target for in vivo gene-editing therapies, such as NTLA-2002, which utilize CRISPR/Cas9 technology delivered via lipid nanoparticles to the liver (Source: Intellia Therapeutics). By targeting the KLKB1 locus within the nuclei of hepatocytes, these therapies induce double-strand breaks that are repaired via non-homologous end joining, resulting in permanent gene disruption and a significant reduction in circulating plasma kallikrein levels (Source: NEJM, Longhurst et al., 2024). This approach aims to provide a durable, one-time treatment to prevent HAE attacks by addressing the underlying genetic driver of bradykinin overproduction (Source: Nature Communications, 2023).

Other names

Kallikrein B1Plasma prekallikrein geneFletcher factor geneKLK3Prekallikrein gene

CRISPR/Cas9-mediated gene knockout via non-homologous end joining (NHEJ) to permanently disrupt the KLKB1 gene and reduce plasma kallikrein protein expression.