Development of Topical Gene-Therapy for Congenital Ichthyosis using engineered-Virus-Like-Particles (eVLPs)

Development of topical gene therapy for congenital ichthyosis using herpes simplex virus based engineered virus-like particles (eVLPs)

Summary of the Project

To explore the use of gene-editing tools including base-editing and prime-editing with an engineered virus-like particle (eVLP) herpes simplex vector to transfect the skin in order to develop a topical gene-cream to treat epidermolytic ichthyosis and other congenital ichthyoses. The primary target for gene-editing is the DNA of the skin stem cells located in the base layer of the epidermis. The secondary objective is to explore the necessary treatment regimen to achieve curative treatment associated with topical application of the gene cream.

Genetic variant included in the Project

• Epidermolytic Ichthyosis Pathogenic Variant on KRT10

Main outcomes anticipated from the Project

We anticipate three major outcomes from this project:

1. The gene editing machinery (such as spCas9, cytosine and adenine base editors) will be fused to the HSV tegument proteins and will maintain gene editing activity in cells;

2. The fusion protein will be packaged into HSV based virus-like particles (eVLP) which will be able to deliver gene-editing activity with high efficiency;

3. Gene variation in ichthyosis patients’ skin cells will be corrected following the delivery of eVLPs packed with gene editing substances.

Project Update: March 2026

Presentation at the EI Global Symposium, Zurich, Switzerland

Dr Amadeus Xu, employed as a postdoctoral research fellow at University College London (United Kingdom) for this project, presented work from the first half of his 2-year research project with Professor Wei-Li Di and Professor Gill Elliot, at the EI Global Symposium which took place in Zurich, Switzerland on 19th March 2026. Dr Xu delivered an engaging talk to explain the current healthcare landscape for gene-editing in skin, and then went on to explain the different approaches to gene-editing for EI. The first half of Dr Xu’s talk is shared with us in the video below, the remainder of the talk is considered ‘Preliminary material’.

Dr Xu then went into greater detail on his project to explain the process of extracting the disease-causing proteins from the Herpes-Simplex Virus, in order to replace them with gene-editing tools designed to correct the EI pathogenic variant.

Dr Xu was happy to report that their project had met all their planned milestones to date and was on track for the next phase of the project, to explore if the modified virus can carry gene-editing tools to the skin stem cells in KRT1 and KRT10 EI models.

We shall eagerly await the next and final update from this brilliant team of researchers.