Abstract

Drug development is a notoriously slow, arduous, and costly process due to high attrition rates. CRISPR-based gene editing can accelerate and improve this in particular with the identification and validation of new drug targets. During screening, knockout of protein function is a convenient way to assess hundreds or thousands of genes for links to disease traits.
For this Synthego has developed an arrayed single guide RNA (sgRNA) library format in which each gene is strategically targeted by multiple guides (multi-guide, patent pending). Conceptually, each multi-guide sgRNA cocktail deletes a fragment in a well-chosen exon of the respective target gene. This typically results in functional knockouts and allows for complex phenotypic assays and read-outs. Moreover, Synthego has developed a highly automated platform for CRISPR /Cas9 gene-editing processes at scale. This platform combines a high degree of functional knockout and reliable reproducibility with the ability to process many gene edits simultaneously. This gain in bandwidth can be used for example to look at many targets in a pathway, validate targets across several cell lines or remodel a large number of observed genetic variants in relevant cell lines. Leveraging the insights derived from detailed genetic analysis these capabilities enable to improve the efficiency and quality of drug target identification and validation.