When man meets machine
Scientists and robots work side by side to transform OXGENE’s gene editing solution.
In September this year, OXGENE™ announced the extension of its strategic gene editing partnership with Abcam. To deliver this contract, OXGENE™ is using its high throughput gene editing platform to deliver over 1,000 custom-engineered cell lines over the next three years.
CRISPR based gene editing has been a staple technology of both academic and commercial genetics labs ever since its ability to precisely and permanently modify the genetic code was first described less than ten years ago. It’s a technology with enormous potential to impact the entire scientific spectrum from drug discovery to direct therapeutic applications.
Yet despite its popularity, it’s still relatively early days for CRISPR. Traditionally, many of the steps involved in a successful gene editing project are still time consuming, cumbersome and routinely carried out by hand, which gives plenty of opportunities for errors to creep in.
That’s where OXGENE stands apart. Our highly optimised and quality assured automated CRISPR cell line engineering workflow is built on the foundations of a strong multidisciplinary framework. We’ve brought together expertise in biology, informatics and automation to create a robust and efficient high throughput genetic engineering platform to meet the ever-increasing demand for custom cell line manufacture.
From left to right, Group Leaders Pela Derizioti and Simon Pollack
But it didn’t 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.” says Group Leader, Pela Derizioti, who leads OXGENE’s Gene Editing Platform group. And yet, Pela’s team now routinely produces tens of CRISPR knockout (KO) cell lines a month, with staggeringly impressive success rates.
“I’m incredibly proud of our team here, and what they’ve achieved,” she adds. “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.”
“It hasn’t been easy,” says Simon Pollack, Group Leader of the Laboratory Automation team at OXGENE. “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 realise 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.”
So how do you go about building a high throughput gene editing platform?
“Piecemeal!” answers Simon. “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 optimising 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.” Pela notes. “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.”
Despite the obvious pride that both Pela and Simon have in OXGENE’s high throughput platform, neither of them are resting on their laurels. “There’s lots more to do. The next steps for us are to optimise conditions for more complex cell types, like primary cells and stem cells, and also more complex modifications, such as knock-ins.” Pela says.
“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.” chips in Simon, “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.”
And increased capacity drives R&D, notes Pela. “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.”