Vertical integration of CRISPR/Cas9 in drug discovery

Supported by:

2 February 2017

Once in a while discoveries are made that greatly impact the world. In the biology field, the CRISPR/Cas9 system is such a revolutionizing technology that brought rapid, efficient and precise genome engineering in a variety of species within reach of many researchers. The beauty of the system lies in the use of guide RNAs(gRNAs) that direct the Cas9 endonuclease to a specific site in the genome where it induces a double-stranded break. The repair of this break allows a gene editing event either via the non-homologous end joining (NHEJ) or homology-driven repair (HDR) pathway.

Since its discovery as a genome engineering tool in eukaryotes in 2013, the research field has embraced this technology for different applications ranging from basic research into gene-function relationships to the potential use for gene therapy. In this webinar, the speaker will focus on the utilisation of CRISPR/Cas9 technology in drug discovery, with an emphasis on generation of in vitro models for high-throughput screening, and creating new mouse models.

Several CRISPR/Cas9 case studies will be discussed during this webinar covering different aspects of the drug discovery process. One example is the integration of a transgene into a safe harbor locus of the HEK293 cell line using a single-stranded oligo donor as repair template. Other case studies focus on the generation of knock-out or single nucleotide polymorphism (SNP)-corrected mice by CRISPR/Cas9 gene editing of mouse embryonic stem cells (mESC) using the NHEJ and the HDR repair pathway and subsequent injections of the targeted mESC into blastocysts. CRISPR/Cas9 technology was also applied for gene editing of mouse tumor cell lines to generate syngeneic mouse models matching human tumors, using a two gRNA approach to delete an entire exon for full knock-out of the targeted gene. Future activities of Charles River in the field CRISPR/Cas9 will expand to the use of gRNA libraries for target discovery, similar to the Charles River SilenceSelect® RNAi interference technology.