Optimize, Adapt and Overcome - 40

Optimize, Adapt, and Overcome: Tips from the Cell Line Development Front * How to Improve Cell-Line Productivity

additional modification and customization of
protein production cell lines.
For example, glycosylation patterns of expressed
therapeutic antibodies can significantly impact
the pharmacokinetics of monoclonal antibodies and antibody-dependent cellular cytotoxicity (ADCC) activities, making them an attractive
knockout target. The ability to customize your
cell line by knockout of glycosylation pathways
or other factors affecting the efficacy or effectiveness of the desired gene product is a potential
game-changer.
Ms. Holroyd
CRISPR/Cas9 technology allows for a cost-effective high-throughput screening method (for example, pooled CHO CRISPR libraries) to identify
novel targets by allowing a deeper and broader
screening approach. Therefore, CRISPR can serve
as a tool for target identification as well as target
validation.
Orthogonal gene-editing technologies such as
zinc finger nuclease technology can then be
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employed to precisely modify the validated sites
to generate a final bioproduction cell line. Such
precise modifications will lead to better understanding of cellular metabolism, and this better understanding will in turn translate to even
higher efficiencies in productivity and protein
quality.
Dr. Fisch
The combination of data from next-generation
sequencing and bioinformatics along with
CRISPR/Cas9 will have a profound impact on the
development and manufacturing of recombinant
protein drugs. Selexis has developed bioinformatics
tools to assemble the genome of its CHO-K1
cell line.
The direct outcome from this effort? Selexis can
now fully characterize, fully trace, and determine the clonality and integrity of a transgene
sequence, or any other genes, that may play a
role in the stability of its research cell banks. This
work also allows the identification of viral sequences (adventitious agents) present in Selexis'
CHO cell.

Technologies such as CRISPR/Cas9 will allow
Selexis to create a novel, viral-free CHO cell
line that can mitigate the risks associated
with the presence of viral particles in today's
manufacturing process.
Dr. Powers
The key element that gene-editing technologies
(such as CRISPR/Cas9 and transcription activatorlike effector nucleases) bring to the future of cellline development is well captured in the phrase
"precision genome engineering." The ability of
these technologies to precisely target specific
genes for creation of knockouts and knockins,
the correction of mutations, and the introduction
of other modifications has enabled the creation
of cell lines that would have previously been
considered virtually impossible.
We are already seeing this have a dramatic
effect in the creation of cellular models of
disease. And the approach is starting to
emerge as an important element in the
development of future cell-based
therapies. n

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Optimize, Adapt and Overcome

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