Development of Topical Gene-Therapy for Congenital Ichthyosis using engineered-Virus-Like-Particles (eVLPs)
Professor Wei-Li Di and Professor Gill Elliot
Project Duration: 2 year Post-Doctorate; Project Start date: 20th December 2024
Total Project Cost: £152,000
EI Cure Project Award: £83,300; Project Collaborators: University College London and University of Surrey
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:
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;
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;
Gene variation in ichthyosis patients’ skin cells will be corrected following the delivery of eVLPs packed with gene editing substances.