Joanna Gawden-Bone, Manager, Cell Based Screening, Horizon Discovery will explain how leveraging CRISPR-Cas9 technology to perform functional genomic screens provides a powerful boost to elucidate gene functionality in the context of disease and drug discovery.
In this webinar she will discuss:
Considerations around the use of different CRISPR-Cas9 modalities
Comparison of pooled vs arrayed CRISPR-Cas9 Screening
Different formats of CRISPR-Cas9 screening approaches to answer a variety of research questions
CRISPR-Cas9 screens, by allowing efficient homozygous gene knockout, have improved reproducibility relative to RNAi screens and have become the gold standard in functional genomics. The adaptation of the system, by the use of a nuclease inactive form of Cas9, dCas9, has broadened its application by allowing genetic modulation of endogenous gene expression.
CRISPR interference screens suppress gene expression by the recruitment of repressors complexed with dCas9. Whereas, in CRISPR activation, CRISPR-dCas9 specifically target gene activators to sgRNA directed loci. Indeed, combinational screening with these different approaches can further strengthen screen results by providing direct validation of gene behavior via different CRISPR-Cas9 screening technologies. As the technology advances it continually broadens it applicability to address more complex biological questions. The drug discovery pipeline has much to gain from utilizing CRISPR-Cas9 screening at any stage of development, from mechanism of action studies to patient stratification. The choice of screen; pooled or arrayed, and the choice of CRISPR-Cas9 technology, depends on the question being asked, the material to be tested (from cell lines to organoids) and the functional read-out required.