CRISPR technologies have changed the ball game
During the last years, genome engineering of CHO production hosts has played a significant part in improving the yield and quality of therapeutic protein products.
Why is that? Simple answer: CRISPR-Cas9, a system for targeted genome editing.
“Firstly, it has really improved our ability to specifically target the genome, thus, minimizing the difference between different cells. We can for example target genes to improve the quality of the product, such as host cell proteins that degrade the product or its attached glycan structures,” says Co-PI for CHO Cell Line Engineering at the Novo Nordisk Foundation Center for Biosustainability, DTU, Helene Faustrup Kildegaard.
She further emphasizes that the Center has been a frontrunner when it comes to implementing the new technologies.
Improving biotherapeutic production
CHO cells’ rapid rise in production prominence is due to their adaptability to various culture conditions, gene plasticity, and ability in proper folding, posttranslational modifications, and glycosylation of desired proteins.
Thus, advances in CHO cell lines and culture continue to significantly improve biotherapeutic production.
“This achievement is due to progress in engineering stable and transient cell lines, enhancing cell culture conditions and performance, as well as optimizing process development. When all are accomplished it means higher-production titers and better products,” says Helene Faustrup Kildegaard.
Conventional methods to modulate gene expression have generally employed less specific genetic approaches but the new technologies have made the process of making production cell lines more simple and efficient. It will, for example, in the future mean that the time it takes to make a production cell line will be shortened from eight months to four months.
No doubts anymore
The CRISPR-Cas9 system is revolutionizing genomic engineering and equipping scientists with the ability to precisely modify the DNA of essentially any organism. This gene editing could potentially confer genetic advantages that previously took large amounts of time, taxing genetic breeding strategies, or bulkier and more complex genomic editing tools to acquire.
However, when the CHO Cell Line Engineering group started to use the CRISPR technology in the first place some people questioned this decision. But now the critics are left silent in the corner.
“When I am traveling to conferences all over the world, I am all of a sudden ‘the CRISPR woman’”
Helene Faustrup Kildegaard, Co-PI and Senior Researcher
“Our publications on CRISPR are quoted by many and also used by the industry. When I am traveling to conferences all over the world, I am all of a sudden ‘the CRISPR woman’. I will not take any credit for the technology because we didn’t develop it but we have been very good at applying it to our scientific field. A lot of people are actually still surprised how much we use CRISPR in biotechnology,” emphasizes Helene Faustrup Kildegaard.
According to her, as one of the main drivers for the CHO systems biology era, genome engineering with CRISPR-Cas9 will pave the way for rational design of CHO cell factories.