Published researchpublishedPrincipal foundation · CrGO-897 (CMLase)
The original CrGO-897 report
Trabosh N, Smith J, Hsu MY, Panja S, Nagaraj R, Olsson N, McAllister FE, Cravens A. Reversal of protein chemical aging by enzymatic deglycation. Nature Communications. 2026 Jul 14; 17(1):5926. PMID: 42448719. doi:10.1038/s41467-026-75141-2 ↗
The principal foundation of the CMLase research field: the peer-reviewed report of the engineered enzyme CrGO-897 (CMLase), developed by external researchers at Revel Pharmaceuticals, Calico Life Sciences and the University of Colorado Anschutz, which demonstrated enzymatic deglycation of protein-associated CML under controlled laboratory conditions.
- Enzyme origin — CrGO-897 was developed from an FAD-dependent glycine-oxidase scaffold found in Calidithermus roseus, identified through structural and sequence mining.
- Directed evolution — a large-scale computational screen followed by five rounds of directed evolution (over 500 million variants screened through lysine-auxotroph selection) produced activity against the CML side chain, with 15 amino-acid substitutions and a 2-amino-acid deletion relative to the parent enzyme.
- Substrate testing — activity was characterised against free CML, CML-bearing peptides and the model protein CML-BSA.
- Isolated human lens proteins — on long-lived human lens proteins from a 64-year donor, measured CML was reduced by 45% (LC-MS/MS) and 78% (ELISA).
- Prepared human arterial tissue — in prepared human abdominal aorta from a 75-year donor (FFPE immunohistochemistry), measured CML was reduced by more than 70%.
- Prepared human skin tissue — in prepared human skin from donors aged 20–75 years, measured CML was reduced by approximately 55%.
- Reaction mechanism — oxidation of the ε-nitrogen of the CML side chain, restoring native lysine and generating glyoxylic acid (glyoxylate) and hydrogen peroxide.
- Scope of the evidence — every tissue result was obtained ex vivo, in homogenates or thin prepared sections; no living-organism study was performed. The authors note that recovery of tissue mechanics and RAGE-signalling effects in vivo remain unshown, that the bacterial origin raises immunogenicity questions for any repeat dosing, and that catalytic efficiency remains below that of evolved natural PTM-editing enzymes.