Epigenetic reprogramming startup identifies multiple sets of transcription factors with potential in liver disease and immune dysfunction.
As Life Biosciences prepares for ‘world first’ clinical trials this year, excitement around epigenetic reprogramming is building, and another company working in the space has recently made some interesting progress. San Francisco-based NewLimit has revealed its researchers have discovered new transcription factor sets that restore youthful functionality to both hepatocytes (liver cells) and T cells, a critical component of immunity.
Co-founded by Coinbase CEO Brian Armstrong, NewLimit is focused on epigenetic reprogramming to extend human healthspan and treat age-related diseases. Having secured a $40 million Series A financing, on top of its co-founders’ initial $110 million investment, the well-funded company has prioritized the aging immune system and liver as its initial areas of focus.
In a blog post outlining recent progress made by NewLimit, head of research Jacob C Kimmel revealed that the company has identified three transcription factor sets demonstrating pre-clinical efficacy in animal models of liver disease, as well as three sets capable of rejuvenating aged T cells. An additional ten transcription factor sets have been shown to make old T cells resemble young ones in terms of gene expression.
Using single-cell multi-omics tools and machine learning, NewLimit’s discovery platform integrates single-cell genomics, pooled perturbation screening and computational modeling to identify transcription factors capable of restoring youthful function to aged cells.
The company completed its first reprogramming screens in humanized livers at the end of 2024, leading to the discovery of transcription factor sets that not only make aged hepatocytes appear younger but also restore their function. A lead candidate, formulated into a prototype LNP-mRNA medicine, demonstrated the ability to enhance liver regeneration and resilience in pre-clinical models of liver disease. This was further tested in an ethanol injury mouse model, simulating alcohol-induced liver damage, where treated livers exhibited near-youthful levels of resilience.
“These functional results suggest that making old hepatocytes look young is a reasonable way to discover reprogramming payloads that make old hepatocytes act young,” said Kimmel. “It’s hard to imagine better motivation to scale our screens!”
NewLimit has since significantly improved its humanized liver screening system, increasing bandwidth by a factor of 20, enabling the company to evaluate a greater number of transcription factor sets in each experiment.
When it comes to T cell function restoration, Kimmel said that NewLimit has successfully identified three transcription factor sets that restore youthful killing activity in aged CD8 T cells, which play a critical role in immune defense, targeting infected and cancerous cells. Pre-clinical validation, again using prototype mRNA medicines, confirmed that reprogrammed T cells were more effective at eliminating target cells, aligning with the performance of young T cells.
“We believe this is the first demonstration that partial reprogramming can rescue human CD8 T cell function,” said Kimmel.
It’s not clear exactly when NewLimit might join the likes of Life Bio in clinical trials, but the company has always said its mission to “significantly extend” human healthspan is a 20-year endeavour. So, while we may have to wait a while yet for human studies, we continue to follow progress at the company with great interest.
