Although hLYZ possesses a range of advantageous properties,the wild type protein has inherent limitations that pose potential roadblocks to clinical translation.
For example,in pulmonary infections, hLYZ’s cationic character is known to drive electrostatic mediated aggregation with and inhibition by negatively charged biopolymers that accumulate in the infected lung (e.g., DNA, F-actin, mucin, and alginate). To address this limitation, hLYZ’s electrostatic potential field has been
redesigned,and the engineered variant has shown improved efficacy in a murine model of Pseudomonas aeruginosa lung infection. More generally, this successful redesign of hLYZ has led us to conclude that putative limitations of the
wild type protein can be addressed through molecular engineering of performance enhanced variants.