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20 November 2019

Industry overview

Cell and gene therapy: an industry overview

Beyond the scientific difficulties involved in developing a new class of therapies, let alone one that involves fundamentally altering an individual’s genetic code, there are substantial logistical difficulties involved in manufacturing cell and gene therapies. The manufacturing and supply chain isn’t yet standardised, which increases the cost and complexity of production. And of course, these costs eventually trickle through to the patient, resulting in a paradigm shift in the cost and economics of treatment.

Unsurprisingly, companies developing cell and gene therapies are beginning to set their sights on diseases with larger patient populations, such as haemophilia and muscular dystrophy. These represent the best possibility of generating a large return on the investment required to develop these treatments. However, they also require systemic administration of viral vectors, which in turn requires a huge volume of viral particles. And at the moment, the industry simply doesn’t have the capacity to meet this demand using existing technologies and infrastructure.


Scale up vs. scale out

Industry is never static, and companies supplying the essential inputs for manufacturing gene therapies are constantly adapting. There are currently major shifts towards standardising process inputs, for example plasmid DNA, media, purification modules etc, as well as attempts to scale up, rather than scale out production.

Scale out refers to the industry’s initial attempts to maximise viral vector production using adherent cell cultures. Basically, the bigger your available cell culture surface area, the higher viral titre you would command. However, it didn’t take long to realise that this was not a sustainable strategy. It’s inefficient, costly and severely hampered by bottle-necks in the supply chain.

Now, the industry buzz-word of the moment is ‘scale up’, as opposed to ‘scale out’. This has become synonymous with the development of suspension based cell cultures to enable larger reactions without the corresponding requirement for ever more cell stacks, or the impact on laboratory surface space. Scaling up is not without problems however. In this case, it’s limited by efficiency.


Licensable AAV and lentiviral production platforms

OXGENE has hit on a promising solution to this dilemma. A fully-licensable AAV or lentiviral production platform that can be licensed for use in any facility of your choice, and includes all the materials, protocols and intellectual properly involved in the production process. We combine expertise in molecular engineering, cellular biology and bioprocess development to offer a platform that spans all the way from DNA design, through optimising viral vector production, to downstream process development to support scalable manufacture. But above all, we recognise that every customer has unique capsids, transgenes, equipment and protocols they use in their viral vector production process, so we work together with our customers to evaluate, optimise and tailor our platform for each customer’s requirements.


Optimising cell culture to minimise production costs

As the industry struggles to minimise production costs for gene and cell therapies, optimising cell culture to minimise the risks involved in eventual regulatory compliance becomes an important consideration. Again, OXGENE’s viral vector production platforms offer solutions.

Traditional methods of viral vector production involved using SV40 transformed HEK293 cells to boost viral vector expression. However, there are safety concerns around the use of SV40 in gene therapies, so OXGENE’s suspension HEK293 cell lines, which all lack the SV40 T-antigen, sidestep this issue.

In addition, although many of the new materials the cell and gene therapy industry are working with are new, and previously unregulated, in some ways that makes it even more critical to use cell lines with clinical provenance and full traceability whereever possible. All OXGENE’s viral vector production platforms use fully traceable, GMP-banked, animal component free suspension HEK293 cell lines to help further smooth the path to eventual regulatory approval.

Another way to minimise manufacturing costs through cell culture optimisation is through the development of packaging and producer cell lines. This requires that the cytotoxic viral genes be under the control of an inducible promoter when they are introduced into a cell line, but by doing this the cost and complexity of viral production can be significantly simplified becuase the number of transfection steps and plasmid inputs are reduced. OXGENE now have fully licensable lentiviral packaging cell lines, and are well on the way to AAV packaging cell lines too. These packaging cell lines will then form the basis for generation of producer cell lines.



Overall, the cell and gene therapy industry is sandwiched between opposing forces of challenge and opportunity. The promise and the opportunities are tremendous, but so are the challenges. The good news is that now those challenges are well understood, so there’s a clearly defined roadmap for companies like OXGENE who solve problems and offer solutions that bridge the gap between drug development and full scale pre-clinical and clinical manufacture.