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,16,17 and the engineered variant has shown
improved efficacy in a murine model of Pseudomonas aeruginosa
lung infection.18,19 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