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

Projektinformationen

TargetNCREs

ID Finanzhilfevereinbarung: 101138903

DOI

10.3030/101138903

Projekt abgeschlossen

EK-Unterschriftsdatum 25 März 2024

Startdatum 1 Mai 2024

Enddatum 31 Oktober 2025

Finanziert unter

• European Research Council (ERC)

Gesamtkosten

Keine Daten

EU-Beitrag

€ 150 000,00

Koordiniert durch

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)

Berichtszeitraum: 2024-05-01 bis 2025-10-31

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

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.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

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.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

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.