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

Información del proyecto

TargetNCREs

Identificador del acuerdo de subvención: 101138903

DOI

10.3030/101138903

Proyecto cerrado

Fecha de la firma de la CE 25 Marzo 2024

Fecha de inicio 1 Mayo 2024

Fecha de finalización 31 Octubre 2025

Financiado con arreglo a

• European Research Council (ERC)

Coste total

Sin datos

Aportación de la UE

€ 150 000,00

Coordinado por

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)

Período documentado: 2024-05-01 hasta 2025-10-31

Resumen del contexto y de los objetivos generales del proyecto

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.

Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha

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.

Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha)

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.