CRISPR-ing VIB: how cas9 is slicing up VIB’s favorite genes

CRISPR Genome Editing technology is being hailed as the biggest breakthrough life science technology of the century. When combined with access to cheap, synthetic DNA, it is taking us into a new era of biotechnology. VIB’s Tech Watch has boosted many Genome Engineering projects. In this article, we will highlight examples that show how VIB scientists have adopted these technologies.

Genome editing of mammalian cells is made easy with CRISPR. Custom KO/KI cell lines can be generated rapidly, helping to speed up the functional analysis of favorite genes. Wenting Guo of the Ludo Van Den Bosch and Wim Robberecht Lab (VIB/KU Leuven) has used CRISPR to make custom, genome-edited cell lines. As they explain, “with the custom iPS cell lines, I could spend more time focusing on phenotype investigation in the cell lines. Since ALS is a complex genetic disease, correcting the point mutation in ALS-patient derived iPS cells gives us perfect control with the same genetic background to test how the mutation causes cellular defects. It is a powerful technology to model ALS in a dish”.

Petra Van Damme of the Kris Gevaert Lab (VIB/UGent) is working with HAP1 haploid cell lines, in which genes can be rapidly inactivated by CRISPR: “Our studies focus on protein N-terminal modifications and typically used to rely on knockdown studies. However, only suboptimal substrates were identified, likely resulting from the high efficiency of the modification reactions and incomplete enzyme knockdown. HAP1 KO cells will allow us to obtain proteome-wide views of the N-terminal modification landscape”.

The speed, ease and low cost with which CRISPR allows the generation of KO/KI mouse models is also accelerating the study of gene function in vivo. Tech Watch has supported a spectacular uptake of CRISPR in the generation of new mouse models. Jens Staal of the Rudi Beyaert Lab (VIB/UGent) has used CRISPR to make many mouse KI models: “The genome editing revolution is here. We can now rapidly generate mutant mice to study the physiological role of a single amino acid residue on a protein expressed from the endogenous gene, an endeavor that was much more difficult and timeconsuming with homologous recombination”.

In plants, CRISPR is being used to knock out genes and for functional genomics. Geert De Jaeger (VIB/UGent) has used Tech Development funding to tinker with CRISPR so that it can be used as a novel tool to study protein-DNA interactions. Geert comments: “For plant research, I see two milestones thanks to CRISPR technology. First, after decades of fruitless attempts in plants we finally have a tool at hand for targeted knock-out or knock-in. Second, the efficiency of CRISPR in crop plants will boost translational research in Ag-Biotech.”

More info on genome editing here.

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