CRISPR technologies have made significant contributions to biomedical science by enabling researchers to investigate gene function, to study disease mechanisms, and to identify therapeutic targets and develop new treatments. Here are some ways in which CRISPR screens can contribute to biomedical science:

• Gene function and disease mechanisms: CRISPR screens allow researchers to systematically study the function of genes in cellular and disease contexts. By perturbing genes of interest and observing the resulting phenotypic changes, researchers can identify genes involved in specific biological processes and disease pathways, identify gene interactions, and gain insights into disease mechanisms. This knowledge enhances our understanding of diseases at the molecular level and helps identify potential therapeutic targets.

• Drug target identification: CRISPR screens provide a powerful approach to identify new therapeutic targets. By screening large-scale gRNA libraries in disease-relevant models, researchers can identify genes whose disruption leads to desirable therapeutic effects, such as inhibition of cell proliferation or induction of cell death. These genes can serve as potential targets for the development of new drugs or repurposing of existing ones.

• Elucidation of treatment resistance: The ability to perturb large numbers of individual genes allows for the identification of genes and pathways that modulate the effects of drug treatments. By using large scale CRISPR screens one can identify genes that upon inactivation enhance drug response or those that upon inactivation cause drug resistance. This strategy allows for the identification of (genetic) biomarkers associated with drug sensitivity or drug combinations that can prevent or revert treatment resistance.

At ScreeninC, our main objective is to enable and accelerate cancer research by providing scientists throughout the Netherlands expert advice and access to a broad range of state-of-the-art technologies for model generation, gene-editing and large-scale genomic screening.

Our expertise and collection of tools is based on many years of research in which we developed and implemented large-scale functional genomic and small molecule screening technologies in a variety of studies. Alongside our own research programs, we actively work on new technology development and implementation of novel platforms that have recently been developed by others, including CRISPRa, CRISPRi, and assays involving high-content imaging.

Selected publications:

• Van der Noord et al. Systematic screening identifies ABCG2 as critical factor underlying synergy of kinase inhibitors with transcriptional CDK inhibitors. Breast Cancer Research. 2023
• Wang et al. cFLIP suppression and DR5 activation sensitize senescent cancer cells to senolysis. Nature Cancer. 2022
• Hong et al. cGAS-STING drives the IL-6-dependent survival of chromosomally instable cancers. Nature. 2022
• De Rooij et al. A loss-of-adhesion CRISPR-Cas9 screening platform to identify cell adhesion-regulatory proteins and signaling pathways. Nature Communications. 2022
• Zhou et al. A synthetic lethal screen identifies HDAC4 as a potential target in MELK overexpressing cancers. G3. 2021
• Jin et al., EGFR activation limits the response of liver cancer to lenvatinib. Nature. 2021
• Schukken et al. Acute systemic loss of Mad2 leads to intestinal atrophy in adult mice. Scientific Reports. 2021
• He et al. Integrative analysis of genomic amplification-dependent expression and loss-of-function screen identifies ASAP1 as a driver gene in triple-negative breast cancer progression. Oncogene. 2020
• Koedoot et al. Uncovering the signaling landscape controlling breast cancer cell migration identifies novel metastasis driver genes. Nature Communications. 2019