PASylated hyperactive DNase I

PASylated hyperactive DNase I is a long-acting recombinant enzyme therapeutic being developed by XL-protein in collaboration with Rentschler Biopharma. The drug candidate consists of a hyperactive variant of human Deoxyribonuclease I (DNase I) fused to a PAS (Proline-Alanine-Serine) polypeptide sequence. This PASylation technology significantly increases the hydrodynamic volume of the protein, thereby extending its plasma half-life and reducing the frequency of administration. The hyperactive DNase I component is engineered for superior catalytic activity and reduced susceptibility to inhibition by G-actin compared to wild-type human DNase I (dornase alfa). Its primary mechanism of action is the degradation of extracellular DNA (eDNA), which is a key structural component of neutrophil extracellular traps (NETs) and contributes to the viscosity of obstructive secretions in cystic fibrosis and the inflammatory milieu in various autoimmune and inflammatory diseases.

Other names

PAS-DNase IPASylated DNase I