Project: Solving missing heritability in inherited retinal diseases using integrated omics and gene editing in human cellular and animal models

Acronym	Solve-RET (Reference Number: EJPRD19-234)
Project Topic	Inherited retinal disease (IRD) is a major cause of early-onset blindness affecting 350,000 people in Europe. Significant advances have been made in the genomic underpinnings of IRD, which has culminated in novel therapies entering the clinic. Despite this progress, there are important knowledge gaps that hamper a molecular diagnosis in over half of the cases. We and others have provided proof-of-concept for an emerging role of non-coding DNA variation in unsolved IRD, affecting splicing or regulation. Here, we aim at performing a methodological and conceptual shift from classical coding to non-coding genomics. It is our main goal to establish a framework to solve missing heritability in IRD using integrated omics and gene editing in human cellular and animal models. Specifically, we will perform reverse phenotyping and generate cellular models of undiagnosed monoallelic patients with suspected recessive IRD. We will establish an integrative omics framework to accelerate diagnosis in unsolved IRD. Furthermore, we will decipher the regulation of IRD genes in human retina. Integration of omics datasets will improve genome annotation in human retina. We will unravel novel regulatory mechanisms underlying dominant IRD in human cellular and CRISPR/Cas9-generated animal models. Finally, we will transfer research findings to the clinic through ERN-EYE and patient advocacy organizations. Our complementary expertise, track record, and pan-European network offer a unique opportunity to address the unmet need of missing heritability in IRD, paving the way to precision medicine in IRD.
Network	EJP RD
Call	1st EJP RD Joint Transnational Call for Rare Diseases Research Project (JTC 2019)

Project partner

Number	Name	Role	Country
1	UGent	Coordinator	Belgium
2	RUMC	Partner	Netherlands
3	INSERM	Partner	France
4	CUNI	Partner	Czech Republic
5	UNIBAS	Partner	Switzerland
6	TIGEM	Partner	Italy
7	MPIMG	Partner	Germany
8	CSIC	Observer	Spain