Pioneering roots in partial reprogramming. A new chapter taking shape: human application, and wider access to reprogramming and gene therapies.
Journey into the epigenome
A skin cell and a nerve cell carry essentially the same DNA. Yet they look different and do different jobs. What matters is also which instructions each cell uses.
Think of DNA as a library. The sequence holds the information; the cell’s regulatory machinery helps select which pages to read.
Continue the storyDNA wraps around groups of eight histone proteins. These units, called nucleosomes, help organise DNA into chromatin. Packaging and chemical marks help regulate access to the instructions.
We separate the proteins slightly to reveal the structure. Together with the DNA wrapped around them, they form a working unit of the cell’s regulatory machinery.
Continue the storyAcross the genome, patterns of packaging, chemical marks and gene activity help sustain a cell’s identity. As we age, aspects of this landscape change. Some changes may contribute to declining function.
Epigenetic clocks read age-associated patterns. Researchers study those readings alongside cell function to build a fuller picture of biological aging.
Continue the storyPartial reprogramming explores cellular renewal through a temporary intervention. The aim is to recover useful features of an earlier state while keeping the cell’s specialised identity.
Timing is central: introduce reprogramming factors, withdraw them, then follow how the cells respond. Researchers study renewal, identity and function together. The illustration shows the idea of a shift in regulation.
What makes reprogramming partial?The nucleosome is based on the atomic structure PDB 1AOI. The surrounding scenes are conceptual illustrations of DNA packaging and regulation. Our “rewinding” metaphor follows the cell’s changing state, with its DNA sequence retained.
Explore the evidence ↗The epigenome helps organise DNA and regulate gene activity. Its interacting layers give cells different ways to use the same genetic instructions—and give researchers a way to explore changes in cell state.
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Gene activity depends on context: packaging, chemical marks and the proteins present.
DNA carries the genetic information. Epigenetic regulation can change gene activity without rewriting that sequence.
DNA wraps around histone proteins and forms chromatin. Its organisation influences which regions are accessible.
Marks on DNA and histones help shape gene use. Each mark’s effect depends on its location, its neighbours and the role of that region in the cell.
Cellular renewal, with identity at its core.
Full reprogramming can take a specialised cell toward pluripotency: a state with the capacity to give rise to many cell types. Partial reprogramming asks whether a controlled intervention can recover useful features of an earlier state without completing that transition.
Its pattern of gene use supports a particular job.
A temporary input, followed by a period of recovery.
Recover younger features and the original cell identity.
Identity can be temporarily disrupted. Its recovery and function must be measured.
Researchers tune the duration of exposure and the choice of reprogramming factors for the cells they are studying. The goal is to recover youthful features while retaining the identity and function that make each cell useful.
At 199, that scientific conviction drives our next programmes: developing partial reprogramming for human application. This work is taking shape in stealth.
Read the human-cell studyStart with the essentials: how cells change, what we want to restore and why identity matters.
Cells use proteins called transcription factors to help control gene activity. Certain combinations can move a specialised cell toward a different state. In transient reprogramming experiments, the exposure is limited, then the factors are withdrawn.
Recovering features of an earlier cell state. In our library metaphor, the DNA holds the instructions; reprogramming changes how the cell reads and uses them. “Rewinding” describes that change in regulation, with the underlying DNA sequence retained.
A nerve cell carries signals. A skin cell helps build a protective barrier. Renewal matters when cells can continue doing those specialised jobs. That is why researchers track identity and function together during reprogramming and afterwards.
Research in human cells grown in the laboratory and in mice has connected reprogramming with more youthful molecular patterns and improvements in aspects of cell or tissue function. These findings give the field a foundation for developing human applications. Our next programmes build toward that goal.
Our goal is to turn insights about cellular renewal into therapies that improve lives. That work brings together targeted delivery, precise control and meaningful measures of function.
Delivery determines where an intervention acts, how much reaches the target and which other tissues may be exposed.
Study the level and duration of activity alongside cell identity, tissue function and safety.
Connect molecular changes with improvements in function and understand how long those changes last.
Democratising reprogramming and gene therapies is part of the mission.
Gene therapies use genetic material or genetically modified cells to achieve a biological effect. Delivery can help connect a scientific idea to the cells where it needs to work.
Define the biological effect the genetic material is intended to produce.
Protect the payload and reach the tissue where it needs to act.
Control where, how strongly and for how long the intervention acts.
For a therapy to reach more people, the questions extend beyond biology: how it is produced, how consistently it can be delivered, and what it will take to make it affordable. These are part of the future we are working toward.
Reproducible production and a practical path to scale.
Treatment approaches that can work in real care settings.
Wider access as an objective from the outset.
199 is developing its next programmes in stealth. We work closely with Triple Helix and Dr. Patrick Sewell as we pursue human application and broader access.
Discuss our directionPartial reprogramming is our foundation. Our wider interests in cellular senescence and biological measurement inform how we approach aging.
Our wider research includes procyanidin C1 and the biology of cellular senescence. Senolytic approaches investigate the selective removal of senescent cells; they address a different biological question from reprogramming cell state.
Explore the Lonvi PCC1 supplementThrough AgeQuant and biomarker testing, we explore more accessible ways to understand biological aging. Measurement is a tool for asking better questions, and its value depends on how a result connects to health and function.
Explore the discoveries shaping this field, from the structure of a nucleosome to experiments in cellular rejuvenation. The researchers and studies behind each idea are linked below.
Return to the storyThe lab’s information-based theory of aging explores how changes in the way cells read their DNA relate to aging, and whether aspects of that process can be reversed.
The atomic structure behind our molecular illustration: a 146-base-pair DNA fragment wrapped around eight histone proteins.
An analysis of 111 reference epigenomes maps how regulatory features differ across human cells and tissues.
Transient reprogramming restored several youthful molecular features in human fibroblasts grown in the laboratory, alongside increased collagen production and improvements in cell migration. The cells temporarily lost and then recovered their fibroblast identity.
Work in mouse retinal ganglion cells linked OSK expression to changes in epigenetic patterns, regeneration and visual function, connecting molecular reprogramming with tissue-level outcomes.
An introduction to genetic medicines, including approaches to delivering genetic material and modifying cells.