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

Informazioni relative al progetto

TargetNCREs

ID dell’accordo di sovvenzione: 101138903

DOI

10.3030/101138903

Progetto chiuso

Data della firma CE 25 Marzo 2024

Data di avvio 1 Maggio 2024

Data di completamento 31 Ottobre 2025

Finanziato da

• European Research Council (ERC)

Costo totale

Nessun dato

Contributo UE

€ 150 000,00

Coordinato da

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)

Periodo di rendicontazione: 2024-05-01 al 2025-10-31

Sintesi del contesto e degli obiettivi generali del progetto

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.

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

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.

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

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.