Development and Testing of Gene-editing for Epidermolytic Ichthyosis

Development and testing of gene editing for epidermolytic ichthyosis

Summary of the Project

The primary objective is to explore the use of gene-editing tools, including base-editing, prime-editing, and PASTE technology to establish whether it is possible to move from a personalised treatment for a specific phenotype to a ‘One size fits all’ approach for a genotype. The secondary objective is to explore if these gene editing tools can be transfected into the skin with a Lipid-nanoparticle vector, for the eventual development of a gene-cream for topical treatment delivery.

Genetic variants included in the Project

• Epidermolytic Ichthyosis Pathogenic Variants on KRT1 and KRT10 (Results will also be applicable to KRT2)

Main outcomes anticipated from the Project

This project encompasses new gene editing technology to try to develop innovative therapies for EI. To date, there have been no reports of gene editing (base editing or PASTE) for epithelial keratins or EI. Thus, this project will develop a new application for gene editing in skin disease and will create original cell culture models to assess the impact of gene editing correction on skin function (repairing the skin thickening and scaling), as well as exploring the potential to develop a topical gene cream for future clinical testing in EI. Ultimately, this project is about bringing the prospects of correcting the abnormal genes in EI closer to the time when people with EI can engage in clinical trials of "Gene Therapy".

Project Update: September 2026

Recently Published Commentary from PhD Candidate James Williamson and Joanna Jacków

EI Cure Project are delighted to introduce the EI Community to Mr James Williamson, the PhD Candidate working on this important gene-editing project with the brilliant supervision and guidance of Dr Joanna Jacków and Professor John McGrath.

This all-star team are just over 1 year into their 3-year collaborative grant from EI Cure Project and the Rosetrees Trust. They are using next generation base-editing tools to make gene-editing more accessible. With a huge amount of experience with gene-editing in EB already under their belts, they are already showcasing their base-editing skills to the scientific community through this published commentary in response to the following peer-reviewed publication.

Here at EI Cure Project, we thought that this moment would be a great opportunity for our donors and the EI Community to meet James, and to understand the focus of his research a little better.

James explains that his team at KCL are using a new type of gene-editing technology, called base-editing, instead of the better-known CRISPR technology. He explains that performing an edit with CRISPR requires both strands of DNA to be cut, leaving both DNA strands untethered. This can lead to unwanted changes in the DNA sequence which can subsequently lead to the development of new diseases.

James compares CRISPR to base-editing, and explains that base-editing has two benefits: 1) Base-editing makes gene editing more accessible because multiple EI-causing variants can be edited with the same treatment; 2) Base-editing has a better safety profile because only one strand of DNA is cut, which minimises unwanted off-target effects.

James tells us that base-editing has shown promise in early clinical trials for EB, and he and his team are hoping for similar success for the EI Community.

This is a very exciting project, and we look forward to more updates from James and his team in the Jacków laboratory at KCL.