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Raising reproducibility standards

Nature's insideView interviews Michael Weiner, Vice President of Molecular Sciences at Abcam on how our technology portfolio can raise reproducibility standards.

​​​Abcam started in 1998 as the go-to source for research scientists to find the world’s best reagents. Since then Abcam has been raising validation standards at an unprecedented scale, championing data-sharing, and continuously looking for ways to streamline science — helping scientists to minimize time, effort, and money wasted in poor-research. In 2011 the company expanded its direct manufacturing of research tools and has since been acquiring new technologies from other biotech companies. A natural match was found in AxioMx, who pioneered methods for producing recombinant antibodies in a matter of weeks rather than months. In November 2015 AxioMx, along with its founder, Michael Weiner, joined the Abcam fold. Now Vice President of Molecular Sciences at Abcam, Weiner explains how the company’s technology portfolio can raise reproducibility standards for the entire field.

Q. What does AxioMx’s in-vitro platform for making antibodies bring to Abcam?

We founded AxioMx five years ago with a plan to increase the speed for making recombinant antibodies. At the time, you could get short strands of DNA made in a day; you could get your entire genome sequenced in a week; but it was still taking four to six months to make an antibody. We set out to get that down to two to three weeks. The technology we started with was a well-validated system called phage display. This involves engineering viruses called bacteriophages, each of which you can think of as a lunar lander with five struts, and on one or more of those struts we put a unique antibody. If you have a billion to a trillion lunar landers, each with a different antibody attached to the strut, we can produce a library of billions of potential antibodies. Then we use a process, called bio-panning, to find the best ones that stick to our target antigen. However, that classic protocol was still a bit clunky, so we found faster ways for each step and created a system that’s 10- to 1,000-times more efficient, and I’m pretty sure we’re the quickest now. We generally make recombinant antibodies in about six weeks, but our record is 19 days from start to finish. That’s pretty fast! And we’re trying to get that down to just 5 or 10 days, which would be incredible.

Q. How does this technology integrate with and complement Abcam’s other platforms?

One of the huge advantages of being acquired by Abcam is their juggernaut of imaging capabilities that we can work with. We can hand off the discovery phage clones from our antibody libraries, and they can tell us which of the dozens of clones is the best one to mature, based on specificity and other properties. So, there’s a real synergy between what we were doing at AxioMx and what Abcam has been capable of. Abcam is the world’s fastest in characterization and we developed some of the fastest ways of making antibodies. It also makes sense following some of Abcam’s earlier acquisitions. For instance, in 2012 Abcam also acquired Epitomics, which makes some of the best monoclonal antibodies for research and diagnostic applications. So, with Epitomics making recombinant monoclonals and us making recombinant antibodies in vitro, it’s almost the complete package of what you’d want in an antibody platform.

Q. Scientists just want an antibody they can trust. What safeguards are in place to ensure consistency and reliability? 

Through production, we can characterize the antibody itself, for example, to make sure the molecular weight is the same. But, Abcam also has a collaboration with a company called Horizon to use CRISPR gene-editing technology to validate the antibodies. That’s kind of a new gold standard. Using CRISPR, we can create a cell line in which the particular protein target of interest has been knocked out. Then we test the antibody’s activity both in those cells and in another cell line in which the protein target is expressed. Any difference provides pretty good evidence that the antibody is hitting the single target that you want it to. We’re really proud of our knockout initiative. It’s really changing the validation field and it’s the best option now for raising validation standards at scale.

Q. An inability to reproduce other scientists’ findings is a significant problem and antibodies are often to blame. What is Abcam doing to tackle this?

Manufacturers have a responsibility to make sure their tools and reagents are what they say they are. That’s one area where I think Abcam has excelled in recent years. For one thing, we are going through the catalogue and making sure our antibodies are functioning as they should. We also have the Abreview program, so scientists can bring the power of social networking to bear on antibody characterization.

Q. Congratulations on recently being named the Connecticut United for Research Excellence’s ‘Entrepreneur of the Year.’ How did it feel to receive that accolade from your peers?

I was really pleased about getting that particular award. Traditionally, it’s gone to either an academic who’s founded a company, or to the CEO who’s grown one. This was the first time it was given to a scientist. The recognition that a scientist — which is what I consider myself — could win was almost more special than seeing my own name on the plaque.

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 Scientists just want an antibody they can trust. What safeguards are in place to ensure consistency and reliability? Through production, we can characterize the antibody itself, for example, to make sure the molecular weight is the same. But, Abcam also has a collaboration with a company called Horizon to use CRISPR gene-editing technology to validate the antibodies. That’s kind of a new gold standard. Using CRISPR, we can create a cell line in which the particular protein target of interest has been knocked out. Then we test the antibody’s activity both in those cells and in another cell line in which the protein target is expressed. Any difference provides pretty good evidence that the antibody is hitting the single target that you want it to. We’re really proud of our knockout initiative. It’s really changing the validation field and it’s the best option now for raising validation standards at scale.