Reversal of protein chemical aging by enzymatic deglycation

Trabosh N, Smith J, Hsu MY, Panja S, Nagaraj R, Olsson N, McAllister FE, Cravens A

1. 01

   CMLase engineered by directed evolution across more than 500 million variants over five rounds

2. 02

   Specifically oxidizes CML and restores the native lysine residue

3. 03

   Removed up to 97% of CML from model proteins in vitro

4. 04

   Reduced CML burden by approximately 45-70% in ex vivo human lens, skin and artery tissue from elderly donors

5. 05

   Establishes that a stable AGE adduct long deemed irreversible is amenable to enzymatic repair

Study Design

Preclinical Study

Sample Size

Not reported

Study Duration

In vitro / ex vivo

Methodology

Enzyme engineering by directed evolution from a bacterial glycine oxidase scaffold; activity validated on model glycated proteins in vitro and on explanted human lens, skin and artery tissue from elderly donors, with mass-spectrometry quantification of CML.

Limitations

Proof-of-concept only. All human data are ex vivo (explanted tissue) - there is no in vivo administration, no delivery route, no pharmacokinetics, no immunogenicity assessment and no functional or clinical endpoint. CML is one of several AGE species; reversing it has not been shown to improve tissue mechanics or any health outcome. Industry-affiliated (Revel Pharmaceuticals, Calico).