Evaluation of non-coding elements as novel therapeutic targets

About 350 million people worldwide suffer from a rare disease. Over 7,000 different rare diseases have been identified, 80% of which have a genetic cause. Recent large-scale sequencing technologies enable a fast and accurate genetic diagnosis, which is a prerequisite for precision medicine.

This project aims to identify non-coding cis-regulatory elements as novel targets for genetic therapy, using inherited blindness as a proof-of-concept. First, we will dissect the non-coding cis-regulatory landscape in the human retina, followed by an in-depth functional study of selected elements. Second, we will evaluate the therapeutic potential of for instance antisense oligonucleotides or CRISPR-Cas9 to modulate these elements. To this end, we will make use of patient-derived induced pluripotent stem cells and differentiate these to relevant models such as organoids, enabling research in the patient’s genetic background.