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On the Horizon

Leading news, knowledge, and industry trends in genetic research

Gene editing

28 result(s)



A number of siRNA and shRNA screens have identified targets that exhibit differential dependencies between KRAS mutant and KRAS wild-type tumours, but there is poor overlap between these published studies. Next generation screens that exploit both isogenic cell lines and cancer cell panels, and use a combination of knockdown (si/shRNA) and knock-out (CRISPR-Cas9-sgRNA) methodologies might be more effective at identifying novel targets that withstand validation. However, if we are to detect co-dependence as well as synthetic lethal interactions, screens must be performed under conditions where mutant KRAS alleles are essential for growth.


The emergence of RAS mutations is a key mechanism of acquired resistance to MAPK-pathway targeted agents in a number of cancers. The preclinical evaluation of targeted agents traditionally relies on panels of genetically unrelated cell lines grown as 2D monocultures. The heterogeneous nature of these panels makes identifying genotype-specific responses a challenge. In addition, 2D assays do not accurately mimic the tumour microenvironment and so add to the difficulty in interpreting which cellular responses to targeted agents will have relevance in vivo.


Much information about the role of specific genes in fundamental biological processes and the onset and progression of genetic disease has been gleaned by researchers having the ability to selectively alter the genomic composition of individual genes and study the consequences. This approach enables researchers to observe the effects of a specific mutation, SNP or deletion in combination with the added layers of regulation present within the cell, including post-translational modification, epigenetic changes associated with chromatin structure, and transcriptional mechanisms.


Thanks to next-generation sequencing (NGS), we are starting to understand the mutational changes that occur across the board in the cancer genome. With this knowledge comes potential - novel mutated genes and the proteins that they encode are candidates for prognostic markers and/or new drug targets.


It’s hard to keep up with the rapidly expanding world of CRISPR, and it’s starting to feel like CRISPR screens are being published every week, taking the technique from the cutting edge to the mainstream. If you’d like to understand a bit more about CRISPR screens, here’s a number of fantastic publications that have really moved this technology forward.