Genome editing allows for ‘faster, simpler’ CHO cell lines

By Ben Hargreaves contact

- Last updated on GMT

(Image: Getty/Panuwach)
(Image: Getty/Panuwach)

Related tags: CRISPR, Gene editing, MilliporeSigma, CHO cell lines

As MilliporeSigma expands its patent portfolio for its genome editing technology, the company’s head of strategy discusses how CRISPR is changing the bioproduction landscape.

Ahead of Biotech Week Boston, MilliporeSigma announced that it had been granted an additional seven patents​ across Europe, Israel, South Korea, and the UK for its CRISPR gene editing technology.

With the acceptance of its patent applications, the company now holds 20 patents across nine different geographies, after receiving its first patent in Australia during 2017.

MilliporeSigma has already begun licensing the technology it has developed through gene editing technology, with genOway agreeing a licensing deal​ late last year.

Gene editing has become a broader topic of discussion, as the reality of its potential uses, and misuses, becomes clearer with the rapid pace of its development. Prompted by misgivings generated by one high-profile case​, a group of companies that are working actively in the area of gene editing recently published a list of principles​ that they would adhere by.

When BioPharma-Reporter (BPR​) spoke to Supriya Shivakumar (SS​), head of Strategy, gene editing and novel modalities at MilliporeSigma, she told us that all of its work is done under discussion with an independent bioethics advisory panel.

Though the technology is often understood to offer potential treatments for genetic diseases, Shivakumar explained how MilliporeSigma is harnessing the technology to improve bioproduction.

Supriya Shivakumar
Supriya Shivakumar, head of strategy, gene editing and novel modalities, MilliporeSigma

BPR: What potential uses could CRISPR have in the biomanufacturing process?

SS:​ CRISPR’s ability to manipulate the genome allows it to develop more finely tuned cell-based assays. MilliporeSigma has used genome editing technology (zinc finger nucleases) to create Chinese hamster ovary (CHO) bioproduction cell lines that have increased efficacy for biopharmaceutical production. MilliporeSigma’s ‘Chozn’ platform is the first-ever commercially available CHO mammalian cell expression system that allows for faster, simpler selection and scale-up of high-producing clones for the production of recombinant protein drugs.

In addition, MilliporeSigma is developing improved cell lines for the production of viral vectors that are used for cell and gene therapy. Any step in the process of manufacturing biomolecules that can benefit from a more specific cell-based assay (such as potency, immune response and safety) is a prime target for CRISPR genome editing.

CRISPR integration can be used to engineer a biopharmaceutical to create a more active formulation by creating more efficient folding sequences, secretion sequences or improving other regulatory elements and through compatibility with any variety of host cells. These approaches can also be used to create more personalized therapies.

BPR: Could you outline what MilliporeSigma’s current offerings are in the space?

SS: ​MilliporeSigma was the first to offer custom biomolecules for genome editing globally, driving adoption of these techniques by researchers throughout the world. MilliporeSigma was also the first commercial tool provider to manufacture and offer basic CRISPR products (Cas9 and Cas9-nickases) in custom single-gene and whole genome library formats.

MilliporeSigma sells thousands of CRISPR kits globally to academia, pharmaceutical companies and biotechnology companies. The specific intended use of the genome-editing reagents determines the license that is required. Use of genome-editing reagents for research requires a Licensed Research Use license, which describes the limitations for the use of the product and is often referred to as a ‘label license.’ The label license is the main means to restrict the use of the genome-editing reagents to align with the supplier’s standards.

There are several examples of MilliporeSigma’s contribution to developing new applications for CRISPR technologies, many of which are covered by pending patent applications or granted patents:

  •  CRISPR-assisted integration of exogenous DNA into eukaryotic chromosomes
  • Paired nickases for improving CRISPR specificity
  • Lentiviral CRISPR formats supported by our 15 years’ experience in high throughput lentiviral manufacturing of shRNAs
  • Cas9-p300 fusions for upregulation of gene expression via targeted histone acetylation
  • Cas9-geminin fusions for boosting homology dependent repair by limiting Cas9 expression to specific cell cycle phases
  • The proxy-CRISPR method for boosting the activity and specificity of almost any CRISPR system in mammalian genomic contexts
MilliporeSigma_CRISPR_Patents_Map
MilliporeSigma CRISPR patents map

BPR: How does the granting of these seven additional patents fit into MilliporeSigma’s strategy in the area?

SS: ​MilliporeSigma is focused on growing its global intellectual property portfolio of CRISPR integration and second-generation technologies.

CRISPR is a tool to help answer researchers’ questions. Having more tools available helps them not only answer their biological questions, but also, MilliporeSigma’s patent portfolio – with more specialized CRISPR methods for increasing specificity and effectiveness – allows them to pose more complex and incisive experiments. Having the intellectual property available means researchers can identify the best tool to answer their questions. This results in less costs. With MilliporeSigma’s toolbox, academics and researchers can start to create the right cell lines to answer their questions, reducing ambiguity for more definitive and actionable results. Driving research leads to a better understanding of biology, and that leads to driving treatments.

BPR: How will genome editing advance into the future?

SS: ​MilliporeSigma believes genome editing holds great promise for understanding and potentially curing even difficult to treat diseases. We support the use of genome editing in basic research in the hopes of discovering new and actionable biological information leading to novel approaches for disease treatment and prevention, including the development of new treatments using approaches for somatic (non-heritable) cells. 

However, we do not support the use of genome editing in human embryos and believe critical safety, ethical, and legal issues exist regarding the application of gene-editing technologies to human germline cells. MilliporeSigma is actively committed to an ongoing thoughtful discussion of genome editing issues via the work of its parent company’s independent, external Bioethics Advisory Panel. Guidance from external bioethical experts is transparently published and translated into MilliporeSigma’s binding policies on genome editing — a contribution to thought leadership in the rapidly evolving field of bioethics in genome editing.

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