Contact Us
Revel Pharmaceuticals
CMLase
An engineered enzyme that reverses Nε-carboxymethyl-lysine — a form of chemical damage that accumulates in the body's long-lived proteins over decades, and was considered permanent for forty years.
What is CMLase?
CMLase is an engineered enzyme developed by Revel Pharmaceuticals that targets Nε-carboxymethyl-lysine (CML), one of the most abundant advanced glycation end products (AGEs) in the human body.
CML forms when sugars react with proteins — the same class of chemistry that browns bread into toast. On short-lived proteins this hardly matters, because the protein is replaced. On the long-lived proteins that make up structural tissue — the collagen in your skin and arteries, the crystallin in your eyes — it accumulates for decades. Since the 1980s, that accumulation has been treated as a fixed feature of aging.
CMLase reverses it. The enzyme oxidizes CML and restores the native lysine residue underneath, leaving the surrounding protein structure intact. It repairs the damage rather than clearing the damaged protein.
How CMLase was engineered
No enzyme in nature is known to perform this reaction. CMLase was built rather than found.
Revel started from a bacterial glycine oxidase scaffold and applied directed evolution across more than 500 million enzyme variants, screening against real substrates rather than predicted ones. That campaign produced the variant designated CrGO-897 — an enzyme with specific activity against CML and, critically, the selectivity to leave undamaged lysine alone.
This is the same discovery and engineering platform Revel applies across its pipeline: screen nature's diversity at scale, find the rare hit, then engineer it into a therapeutic. See how the platform works →
What CMLase did in human tissue
CMLase was tested on ex vivo human tissue from donors aged 20 to 75 — including artery, skin, and lens.
>70%
CML reduction in arterial tissue from a 75-year-old donor
>55%
CML reduction in aged skin — below the level typically seen in 31-year-old skin
20–75
Donor age range across the human tissue panel
Across model proteins, CMLase repaired the majority of damage sites while preserving the integrity of the underlying protein.
The peer-reviewed publication
The CMLase work was published in Nature Communications by scientists at Revel Pharmaceuticals, Calico, and the University of Colorado Anschutz Medical Campus.
Nature Communications · 2026
Reversal of protein chemical aging by enzymatic deglycation
Coverage of CMLase
- The New York Times — “Can This New Enzyme Turn Back the Clock in the Human Body?”
- The Scientist — “Lawnmower-like Enzyme Rewinds Decades of Molecular Aging in Human Tissue”
- Chemical & Engineering News — “Enzyme engineers tackle protein damage from aging”
- Phys.org — “Engineered enzyme erases a stubborn mark of aging by up to 70% in human tissue samples”
CMLase: common questions
Who developed CMLase?
CMLase was developed by Revel Pharmaceuticals, Inc., a San Francisco–based enzyme engineering company founded in 2020, in collaboration with Calico and the University of Colorado Anschutz Medical Campus. The work was published in Nature Communications in July 2026.
What does CMLase actually break down?
Nε-carboxymethyl-lysine (CML), an advanced glycation end product. CMLase oxidizes the CML modification and restores the original lysine residue, rather than degrading the protein it sits on.
Does CMLase reverse aging?
CMLase reverses protein chemical aging. For decades, CML was considered a permanent, chemically stable modification of long-lived proteins. The published work shows an enzyme can remove it from aged human tissue: more than 70% from a 75-year-old donor’s artery, and enough in aged skin to fall below levels typical of a 31-year-old.
That matters beyond the chemistry. CML is a major ligand for RAGE, a receptor linked to chronic inflammation and to many age- and diabetes-related complications, so lowering CML on long-lived proteins could reduce disease burden in aging and in diabetes.
Aging has many causes, and CML is one kind of damage among many, so removing it alone will not reverse aging as a whole. But the platform that built CMLase can be aimed at other damage, including glucosepane, the dominant crosslink in human tissue, which remains resistant to reversal.
Is CMLase available as a treatment?
CMLase is not yet available. It is at the research stage: the published results come from model proteins and donated human tissue tested in the lab, not from treating people. It is not yet an approved treatment, and Revel does not sell it or offer it through any clinic, supplement or skincare product. We’re working toward first human studies and will share news here when there is some. For scientific or partnership enquiries, get in touch.
CMLase and the CrGO-897 enzyme variant were developed at Revel Pharmaceuticals, Inc. Research-stage technology; not an approved medical treatment. For scientific or partnership enquiries, get in touch.