Targeting the dark side of the human genome—non-coding regulatory elements—to treat diseases

Project Information

TargetNCREs

Grant agreement ID: 101138903

DOI

10.3030/101138903

Project closed

EC signature date 25 March 2024

Start date 1 May 2024

End date 31 October 2025

Funded under

• European Research Council (ERC)

Total cost

No data

EU contribution

€ 150 000,00

Coordinated by

ACADEMISCH ZIEKENHUIS LEIDEN
Netherlands

Periodic Reporting for period 1 - TargetNCREs (Targeting the dark side of the human genome—non-coding regulatory elements—to treat diseases)

Reporting period: 2024-05-01 to 2025-10-31

Summary of the context and overall objectives of the project

The 98% of the human genome, sometimes referred to as the dark side of the human genome, contains many non-coding regulatory elements (NCREs), which control the combinational expression of the limited number of genes (only 2% of the genome) to form diverse cell types and tissues of a complex human body, all from the identical copy of the genome. Most genetic variants and mutations also lie in NCREs. However, the number of NCREs as potential therapeutic targets remains very limited. In TargetNCREs, two novel and unique high-throughput screening systems further developed within the ECR starting grant (Silencer) will be exploited for their innovation and commercial potential to harness the therapeutic values of NCREs. We aim to test and validate previously identified top hits in vivo, carry out pilot research to show the technologies to be effective and appropriate for commercial applications, clarify the IPR protection strategy, engage partners and stokeholds to focus on potential pipelines, and perform a market search for future business development.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

We have performed a medium-throughput screening using Technology 1-Silencer with a smaller oligo pool tiling several disease-associated genes and identified potential silencers that may be relevant for therapeutic intervention. We are currently validating a selection of top hits. In parallel, we have designed a screening library to demonstrate that Technology 2—Dual-CRISPR can be applied in a medium-throughput format to identify non-coding regulatory elements. We have conducted market research to identify key disease areas in which these technologies have strong potential for translational impact.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The research conducted under the ERC PoC grant indicates strong potential for both platforms to identify non-coding regulatory elements that could serve as therapeutic targets. Further research and demonstration will be required to showcase the feasibility of these technologies in disease-relevant settings.