Optimisation of cell specific, dual vector delivery for CRB1-associated inherited retinal degeneration.

Brief Lay Background

The CRB1 gene is implicated in a number of vision loss conditions, including retinitis pigmentosa (RP), Leber congenital amaurosis (LCA), cone-rod dystrophy and macular degeneration. Patients with mutations in the CRB1 gene can have different symptoms: while some experience progressive sight loss late in life, others most commonly present at birth or early life with severe retinal degeneration (LCA or RP, respectively).

The CRB1 gene produces CRB1 protein but, unusually, the protein is present in two different forms. Furthermore, these proteins are observed in two different retinal cell types. This causes a difficulty for gene therapy because we need a strategy that enables us to target two cell types to correct/replace two different versions of CRB1. This project aims to tackle and resolve this issue, and its outcomes will enable the development of optimised gene therapy designs for CRB1-associated disease.

What problem/knowledge gap does it help address?

While therapeutic modalities such as gene supplementation therapy have made great strides towards safe and effective clinical implementation for inherited retinal disease, there are some genes that pose challenges to therapeutic development.

For CRB1-associated retinal disease, no treatment currently exists, in part because CRB1 protein is present in two different, functionally important forms that are observed in Müller glia cells and photoreceptors. Cell-specific drivers of gene expression, could be used to achieve cell-specific expression of a treatment technique. 

Aim of the research project

This project aims to optimise the cell-specific delivery to several cell types of the retina to pave the way for successful implementation of gene therapies for CRB1-associated inherited retinal disease.

Potential impact on people with sight loss

Developing and optimising a delivery strategy that will ensure effective delivery of a therapy to both photoreceptor and Müller glia cells is an essential building block towards the successful implementation of a therapy for CRB1-related disease.