Improving CHO Cell Biomanufacturing via Whole Genome CRISPR Screening

This webcast features: Jamie Freeman, PhD, Product Manager, Horizon Discovery

While Horizon’s GS knockout CHO K1 cell line is rapidly becoming established as one of the best performing cell lines available for the manufacture of biotherapeutics, there is untapped potential within the CHO system. Horizon is focused on using its expertise in genome engineering techniques to modify CHO cell lines to improve their expression capacity for biomanufacturing.

Historically, efforts to increase yield have primarily focused on improving media and feed, whereas efforts to identify high productivity clones have been streamlined via improved selection systems. Aside from single gene knockouts to allow for metabolic selection systems, the CHO host line has remained largely unchanged over the past thirty years.

In this webcast, Freeman describes how Horizon identifies and alters genetic targets to improve the biomanufacturing capacity of their high performance GS knockout CHO K1 cell line.

Horizon has designed and optimized a whole genome CRISPR library using a high quality well annotated sequence of their cell line (which is now available as the reference sequence for CHO on Ensembl). In parallel, they have designed FACS based reporter assays that are compatible with both monoclonal antibodies as well as non-mAb products. Together, these allow them to perform whole genome CRISPR screens to identify genetic targets that improve expression from the cells.

Once a gene has been identified and its impact validated, Horizon will use its rAAV-based engineering technology to generate an edited cell line suitable for manufacturing with a clear IP position and the freedom to operate in bioproduction. Improving the CHO cell’s expression capacity for both monoclonal antibodies and more difficult-to-express proteins enables the manufacture of next generation therapeutics that could not previously be achieved using existing solutions.



Leave a Reply