OSK Partial Reprogramming
OSK partial reprogramming (transient expression of Oct4, Sox2 and Klf4)
Written by Aaron CuhaReviewed Sep 2026
Also known as: OSK, Three-factor reprogramming, Yamanaka factors without c-Myc, AAV-OSK, Partial epigenetic reprogramming
Three of the four Yamanaka factors, switched on briefly to reset epigenetic marks without erasing cell identity. Every efficacy result is in mice. One phase 1 safety trial is recruiting, in 18 people, in one eye.
Overview
Partial reprogramming is the idea that ageing cells keep a readable record of their younger epigenetic state, and that turning on a subset of the Yamanaka factors for a short period can recover it. OSK is that subset: Oct4, Sox2 and Klf4, with c-Myc deliberately left out because c-Myc is an oncogene. In a 2020 Nature paper, expressing OSK in mouse retinal ganglion cells restored youthful DNA methylation patterns, promoted axon regeneration after optic nerve injury, and reversed vision loss in a mouse glaucoma model and in aged mice. The effect required the DNA demethylases TET1 and TET2. A 2022 Nature Aging paper extended long-term partial reprogramming to normally ageing wild-type mice and reported reversion of epigenetic clock measures and lower inflammation and senescence gene expression, but made no lifespan claim in those animals.
No human has received systemic OSK. The entire human record is one first-in-human study: Life Biosciences' ER-100, an AAV carrying OSK, injected into one eye of people with open angle glaucoma or non-arteritic anterior ischaemic optic neuropathy, activated by oral doxycycline for 56 days. It is registered as NCT07290244, phase 1, non-randomised, estimated enrolment 18, recruiting since March 2026. Both of its primary endpoints are safety endpoints. It is not designed to show that reprogramming reverses anything in a person, and it has posted no results.
The eye was chosen for a reason. Reprogramming in living animals causes cancer. Transient four-factor induction produced teratomas in multiple mouse organs, and stopping reprogramming part-way produced tumours resembling Wilms tumour in mouse kidney. Confining the therapy to one immunologically privileged, physically compartmentalised, locally dosable organ contains that risk in a way systemic dosing cannot. That is a safety decision, not a sign that the biology is further along.
Mechanism of action
Established in mice. OSK expression drives partial erasure and rewriting of DNA methylation marks, moving the methylation profile of a cell toward a younger pattern without progressing to pluripotency. In the 2020 optic nerve work the benefit required TET1 and TET2, the enzymes that carry out active DNA demethylation, which is direct evidence that the effect runs through methylation rather than through generic transcription-factor activity. In human cells, the only mechanistic work is in culture: keratinocytes expressing OSK showed epigenetic markers of age reversal in the 2024 Cellular Reprogramming paper. Nothing about the mechanism has been demonstrated in a living person.
Human evidence
No human has received systemic OSK reprogramming. One trial exists, it is a phase 1 safety study of a single injection into one eye in an estimated 18 people, it began recruiting in March 2026, and it has posted no results. There is no human efficacy data of any kind.
- NCT07290244, Life Biosciences ER-100: phase 1, non-randomised, sequential dose escalation with a sentinel participant at each dose level and a Safety Review Committee gate, estimated enrolment 18, start date 2 March 2026, status recruiting. Adults with open angle glaucoma are enrolled first, then a dose is selected for a non-arteritic anterior ischaemic optic neuropathy cohort.
- The intervention is an AAV carrying OCT4, SOX2 and KLF4, injected intravitreally into one eye, with systemic doxycycline for 56 days as the switch that turns expression on. Follow-up runs up to five years. Participants provide tears, saliva, faeces and urine for biodistribution and shedding assessment, which is standard for a first-in-human AAV product.
- Both primary endpoints are safety endpoints: incidence of treatment-emergent adverse events and incidence of dose-limiting toxicities, measured from baseline to day 56 and day 112. There is no efficacy primary endpoint.
- Human cells in culture: keratinocytes expressing exogenous OSK showed epigenetic markers of age reversal in the 2024 Cellular Reprogramming paper. That is cell culture, not a person.
- A ClinicalTrials.gov search verified in the source research pass returned zero registered reprogramming trials for Altos Labs, YouthBio Therapeutics, Turn Biotechnologies or Retro Biosciences. Altos Labs is the largest-funded company in the field and has no registered human trial.
What this does not tell you: Nothing here tells you whether OSK does anything beneficial in a human being. A phase 1 safety study in 18 people, dosed into one eye, cannot measure vision restoration with any reliability and is not designed to. It says nothing about systemic dosing, nothing about ageing outside the eye, and nothing about the cancer risk that the mouse literature establishes, because 18 people followed for a few years cannot detect a tumour rate that matters. Every efficacy claim about partial reprogramming currently rests on mice.
Reading the research record
Partial reprogramming is the most heavily funded area in longevity biotechnology and the one with the least human data. Altos Labs launched in 2022 with about three billion dollars and has no registered human trial. YouthBio Therapeutics, Turn Biotechnologies and Retro Biosciences likewise return no genuine reprogramming trial on ClinicalTrials.gov. The single registered study in the world is Life Biosciences' ER-100, which this site also covers under its own entry. The gap between the money and the registry is the most informative fact on this page.
The reason for the gap is the safety problem, and it is not speculative. Two high-profile mouse papers, in Nature in 2013 and Cell in 2014, showed that transient induction of reprogramming factors in living animals produces teratomas across multiple organs and, when reprogramming is started and then stopped, tumours resembling paediatric Wilms tumour. The therapeutic window sits between not enough expression to rejuvenate and enough to dedifferentiate into cancer, it is defined by duration and dose, and it has only been characterised in mice. Dropping c-Myc to give OSK, and injecting into one eye with an oral switch that can be turned off, are both engineering responses to that problem. Neither has been shown to solve it in a person.
One further distinction is worth holding on to, because popular coverage collapses it constantly. The 2016 result that partial reprogramming extends lifespan is in a progeroid mouse, an animal engineered to age prematurely from a specific lesion. Reversing that lesion extends that animal's life without demonstrating anything about normal ageing. The one report of lifespan extension in normal mice is a 2024 paper in 124-week-old males from a single group, measuring remaining rather than total lifespan, and it has not been replicated.
The evidence, charted
Fig. 1 · evidence composition
1of 6 citations (17%) are in people
Counted from the citation list on this page. The Human count is the same number shown in the badge at the top. Both understate any literature larger than the sources we cite.
Fig. 2 · evidence over time
Evidence spans 5 distinct years, 2013 to 2026, counted from the citation list on this page.
Fig. 3 · legal status at a glance
US
Not approved
UK
Approved
AU
Approved
CA
Not approved
Approved in 2 of 4, prescription route in 0, not approved in 2. A jurisdiction's classification is a regulatory fact, not a verdict on the science; see Legal status below for the full text and any notes.
Fig. 4 · dose response
No human dose response curve exists
We draw this figure where the data supports it. For this compound in humans it does not, so the panel stays empty rather than borrowing an animal curve and implying it transfers.
Key studies & citations
- Animal2020
Reprogramming to recover youthful epigenetic information and restore vision
Mouse. Ectopic expression of Oct4, Sox2 and Klf4 in mouse retinal ganglion cells restored youthful DNA methylation patterns and transcriptomes, promoted axon regeneration after optic nerve injury, and reversed vision loss in a mouse glaucoma model and in aged mice. The benefit required the DNA demethylases TET1 and TET2. NIH funded, with non-US government and non-PHS support.
Nature - Animal2022
In vivo partial reprogramming alters age-associated molecular changes during physiological aging in mice
Mouse, physiologically ageing wild-type rather than progeroid. Long-term partial reprogramming regimens produced duration-dependent effects in kidney and skin, with reversion of epigenetic clock measures and reduced inflammation, senescence and stress-response gene expression. The authors make no lifespan extension claim for wild-type mice.
Nature Aging - Animal2024
Gene Therapy-Mediated Partial Reprogramming Extends Lifespan and Reverses Age-Related Changes in Aged Mice
Mouse. Systemically delivered AAV encoding an inducible OSK system, given to 124-week-old male mice, extended median remaining lifespan by 109 percent over wild-type controls and improved frailty scores. Read the number carefully: this is remaining lifespan from very late life in male mice only, from one group, in a specialty journal, and it has not been replicated by the NIA Interventions Testing Program or any independent laboratory.
Cellular Reprogramming - Animal2024
Targeted partial reprogramming of age-associated cell states improves markers of health in mouse models of aging
Mouse. Partial reprogramming targeted at specific age-associated cell states improved health markers in mouse ageing models.
Science Translational Medicine - Animal2013
Reprogramming in vivo produces teratomas and iPS cells with totipotency features
Mouse, and the central safety finding for this whole field. Transitory induction of Oct4, Sox2, Klf4 and c-Myc in reprogrammable mice produced teratomas emerging from multiple organs, dedifferentiated NANOG-expressing cells in stomach, intestine, pancreas and kidney, and circulating induced pluripotent stem cells in the blood.
Nature - Human2026
Evaluating ER-100 for Safety in People With Glaucoma or Non-Arteritic Anterior Ischemic Optic Neuropathy
The only registered human OSK reprogramming trial. Sponsor Life Biosciences Inc., phase 1, non-randomised sequential dose escalation, estimated enrolment 18, recruiting since 2 March 2026. AAV-delivered OSK injected into one eye, activated by oral doxycycline for 56 days. Both primary endpoints are safety: treatment-emergent adverse events and dose-limiting toxicities. No results posted.
ClinicalTrials.gov
Frequently asked questions
Has any human been given OSK reprogramming?
One trial is recruiting. NCT07290244 injects an AAV carrying OSK into one eye of an estimated 18 people with glaucoma or ischaemic optic neuropathy, with oral doxycycline as the switch. It began in March 2026, both of its primary endpoints are safety endpoints, and it has posted no results. No human has received OSK systemically.
Does partial reprogramming reverse ageing?
In mice, OSK restored youthful DNA methylation patterns in retinal cells, regrew optic nerve axons and reversed vision loss in a glaucoma model. In normally ageing wild-type mice, long-term partial reprogramming reverted epigenetic clock measures and lowered inflammation and senescence gene expression. None of that has been measured in a person, and a change in an epigenetic clock is a correlational measure, not a demonstrated health outcome.
Why is the first trial in the eye?
Because reprogramming causes cancer in mice. The eye is immunologically privileged, physically compartmentalised, dosable by local injection and directly measurable, so confining the therapy to one eye contains a risk that systemic dosing would not. It is a safety decision rather than a sign of maturity in the field.
Why is c-Myc left out?
c-Myc is an oncogene. The original four-factor Yamanaka set includes it, and the mouse safety literature on four-factor induction is the teratoma and tumour literature. Dropping c-Myc to give the three-factor OSK set is the field's attempt to reduce that risk, and it is why the one registered human product uses OSK rather than OSKM.