How Automation is Benefiting Gene Editing

OXGENE™ unveiled the extension of its strategic gene editing partnership with Abcam in September last year. In order to effectively deliver this contract, OXGENE is employing its high-throughput gene-editing platform to provide more than 1,000 custom-engineered cell lines over a three-year period.

CRISPR-based gene editing has been a cornerstone technology for both commercial and academic genetics labs since its ability to modify genetic code accurately and permanently was first described under a decade ago. It is a technology with tremendous potential to affect the whole scientific spectrum, from drug discovery through to direct therapeutic applications.

Despite its popularity, CRISPR is still a relatively new technology. Conventionally, most of the steps involved in an effective gene-editing project are laborious, unwieldy, and often carried out by hand - providing many opportunities for human error.

However, this is where OXGENE is able to shine. The company’s highly optimized, quality assured automated CRISPR cell line engineering workflow is built upon the foundations of a robust multidisciplinary framework.

The company combines knowledge and experience in biology, automation, and informatics to create a reliable, efficient, high-throughput genetic engineering platform that is more than able to meet the industry’s ever-increasing demand for custom cell line manufacture.

From left to right, Group Leaders Pela Derizioti and Simon Pollack.

From left to right, Group Leaders Pela Derizioti and Simon Pollack.

However, this did not happen overnight.

If someone had said to me two years ago that we could edit hundreds of cell lines in a year, I’d have said, ‘No way. It’s just not possible.’ Despite this, Pela’s team regularly produces tens of CRISPR knockout (KO) cell lines every month, with remarkably impressive rates of success.

I’m incredibly proud of our team here, and what they’ve achieved. I don’t just mean my lab though. I mean the way the whole company has pulled together to make this work: the biologists, the automation team, the bioinformatics team, and even the commercial teams. Everyone chips in. Everyone goes above and beyond. There’s a real sense of everyone working together to achieve a common goal.

Pela Derizioti, Group Leader of Gene Editing Platform, OXGENE

“It hasn’t been easy,” adds Simon Pollack, Group Leader of OXGENE’s Laboratory Automation team. “It’s taken a lot of hard work, a lot of planning… and the occasional high-stress day to get us to where we are now. This high throughput gene-editing platform represents the culmination of an awful lot of work. But I am proud to look at it and realize just what a slick operation it is. The automation team is fairly hands-off now; everything works as it should, and the scientists can use it efficiently. It’s a good feeling to see the impact of your work on a daily basis.”

When asked about the process of building a high throughput gene editing platform, Simon answers, “Piecemeal! First, we automated the process of scanning plates at high throughput. Then we built the IT infrastructure and procedures to deal with clone verification. That was the first piece of the puzzle. The next ‘a-ha!’ moment was getting the hit-picking properly automated. But the best bit for me has definitely been building and optimizing the user interfaces to make them straightforward enough that the scientists can be completely in control of their own work, without needing input from the automation team.”

We couldn’t routinely produce this many cell lines without automation elements, but it’s not just the robots. It’s the operational aspect too. We work closely with the project management team to plan and resource the platform; precise planning is absolutely required for a project of this size. For example, some cell lines grow faster than others, so we’ve had to plan carefully to make sure there are no clashes following single-cell sorting. Building this platform was a big challenge, and it’s taken some trial and error to get right, but we’ve done it.

Pela Derizioti, Group Leader of Gene Editing Platform, OXGENE

Both Pela and Simon are clearly proud of OXGENE’s high throughput platform, but they both continue to look towards the future. Pela says, “There’s lots more to do. The next steps for us are to optimize conditions for more complex cell types, like primary cells and stem cells, and also more complex modifications, such as knock-ins.”

As for the automation, we’re continually improving our user interfaces and building peripherals to automate more and more of the mundane tasks associated with cell line development. We’re also building the capacity for high-throughput knock-in screening. Basically, we’re building more platforms. Within the year, we’ll have doubled our capacity again.

Simon Pollack, Group Leader of OXGENE’s Laboratory Automation team

Pela notes that this increased capacity is a key driver for further research and development. “Anything we do on a small scale, we’re already thinking about how we’d scale it up and make it high throughput. Whether internal or commercial R&D projects, we’ll perfect them on a small scale and then upscale. We initiate R&D projects ourselves so that we’re constantly checking on and improving our capabilities and what we can offer, but we also work with commercial partners to test something out before we increase the scale. We’ll never finish innovating.”

Acknowledgments

Produced from materials originally authored by Sophie Lutter from OXGENE.

About OXGENE

 

OXGENE™ combines precision engineering and breakthrough science with advanced robotics and bioinformatics to accelerate the rational design, discovery and manufacture of cell and gene therapies across three core areas: gene therapy, gene editing and antibody therapeutics.

Gene therapy: We’re transforming the vision of truly scalable gene therapies into a reality; progressing our industry leading transient gene therapy systems towards alternative technologies for scalable, stable manufacturing solutions.

Gene editing: We have automated gene editing to deliver CRISPR engineered cell lines at unparalleled speed, scale and quality and generate complex disease models in mammalian cells.

Antibody therapeutics: We’re employing a novel proprietary mammalian display technology to discover antibodies against previously intractable membrane proteins.

OXGENE™ works at the edge of impossible in mammalian cell engineering. Our scientific expertise and technology solutions address industry bottlenecks. For more information, please visit www.oxgene.com


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Last updated: Jun 1, 2020 at 3:48 AM

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