Preprint evaluates base editing as a strategy for monogenic kidney disease caused by UMOD variants
Researchers report that base editors corrected a representative UMOD missense variant with up to 83.4% efficiency in cell lines and human 3D kidney tubuloids, restoring normal uromodulin trafficking.
A preprint posted to bioRxiv describes a systematic evaluation of base editing strategies targeting the UMOD gene as a potential therapeutic approach for autosomal dominant tubulointerstitial kidney disease caused by pathogenic UMOD variants (ADTKD-UMOD). This is an untreatable monogenic kidney condition in which misfolded uromodulin protein is retained in the endoplasmic reticulum, where it exerts a toxic gain-of-function effect on tubular cells.
The researchers tested the full spectrum of base editing approaches applicable to the UMOD locus and focused detailed analysis on the p.Cys170Tyr missense variant, a representative pathogenic change. Adenine base editors achieved A-to-G correction efficiencies of up to 83.4% in cell line experiments, and corrected cells showed restored trafficking of uromodulin to the plasma membrane — the normal destination for the protein. The correction was also demonstrated in human 3D kidney tubuloids, which are organoid models that more closely approximate the structure of native renal tubular tissue than standard cell lines.
ADTKD-UMOD is a rare disease with no approved disease-modifying therapies. The results presented here are at a preclinical stage; substantial further development — including assessment of off-target editing, in vivo delivery, and safety — would be required before any potential translation. This work has not undergone peer review and should be treated as preliminary.
Plain-language version
For patients, families, and general readers. Educational only — not medical advice.
Scientists have been studying a rare inherited kidney disease called ADTKD-UMOD, which is caused by a fault in a gene called UMOD. People with this condition produce a misfolded version of a protein called uromodulin, which gets stuck inside kidney cells and gradually damages them. There is currently no treatment that targets the underlying cause.
In a new laboratory study — not yet peer-reviewed — researchers tested a gene-editing technique called base editing, which can make very precise, letter-by-letter changes to DNA. They found they could correct one of the genetic faults responsible for the disease with high efficiency in laboratory cell models and in tiny 3D models of kidney tissue grown from human cells.
This is early-stage, preclinical research. It has not been tested in people, and a great deal more work would be needed before anything like this could be considered as a possible treatment.
This is an educational summary, not medical advice. If anything here raises questions for you, please speak with your GP or a clinical professional.
Sources
Read the original reporting — these are the public sources this summary draws from.
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Primary sourcePreprint bioRxiv (Cold Spring Harbor Laboratory) · 2026-10-16Base Editing as a Therapeutic Strategy for Autosomal Dominant Tubulointerstitial Kidney Disease caused by Pathogenic UMOD Variants