Gene-targeted epigenetic reprogramming to qualify otherwise-discarded kidneys for transplantation
For people with end-stage kidney disease kidney transplantation is still the best and often the only long‑term treatment. Yet, too few donor kidneys are available and many are duboptimal and therefore discarded before reaching a patient. This project brings together a partnership between the University Medical Center Groningen (UMCG) and the biotech company Reno-NL to develop an innovative CRISPR-based epigenetic therapy that restores the low-quality donor kidneys during organ preservation before transplantation.
More than 850 million people worldwide live with chronic kidney disease. In Europe, hundreds of thousands of patients depend on dialysis to survive. While dialysis saves lives, it is expensive, time-consuming, and greatly reduces quality of life. Kidney transplantation is the only curative option. Despite advances such as ex vivo machine perfusion, pioneered at UMCG, a quarter of donor kidneys in the Netherlands is discarded. Current preservation methods can keep organs stable, but they cannot repair existing damage, underlining the urgent need for new solutions.
This project introduces a new way to actively repair donor kidneys before transplantation. In the preservation phase, the project applies a precision epigenetic editing CRISPR tool, delivered using lipid nanoparticles to kidney tissue, to reprogram the expression of genes known to be associated with graft failure.
Unlike irreversible genome editing, epigenetic editing allows durable yet reversible gene regulation, offering a safer and more flexible strategy for use in the clinic. This new approach will increase the number of kidneys available for transplantation, improve patient outcomes, and reduce long-term healthcare costs.
By the end of the project, the consortium will deliver a validated platform for lipid nanoparticle mediated epigenetic editing of donor kidneys. This includes optimized delivery protocols, proven stable gene modulation in relevant in vitro systems and ex vivo kidney tissue, and standardized machine perfusion protocols for short- and longer-term efficacy testing.
