A New Generation of CRISPR Technology

A New Generation of CRISPR Technology
Janice Chen, CTO, Mammoth Biosciences

Janice Chen is very inspiring. At the age of 30, she has not only completed a PhD with Nobel prize winner Jennifer Doudna at the University of California, Berkeley, but she has also helped co-found her own successful biotech company.

Jumping straight from finishing her PhD in 2018 to co-founding Mammoth Biosciences with Doudna, lab mate Lucas Harrington, now CSO, and Trevor Martin, now CEO, Chen is CTO of the company.

Mammoth recently announced it had raised $195 million in financing, bringing its valuation up to more than $1 billion and allowing it to achieve ‘unicorn’ status, an impressive feat considering the young age of the company and the ongoing COVID-19 pandemic.

Chen spoke to Clinical OMICs senior editor, Helen Albert, at the recent Hello Tomorrow conference in Paris about her inspirations, challenges she has overcome and her hopes for Mammoth and CRISPR gene editing in the future.

Was it like to do a PhD with Jennifer Doudna?

It was very cool. Jennifer is a really fantastic scientist and mentor. And I think she’s been able to attract some of the best scientists in her lab. So being not just in the forefront of CRISPR technology, but also working alongside some very talented people. As you know, the CRISPR field is very competitive. I think being able to have the opportunity to continue to push the field forward, that was really remarkable. The other great thing about working in Jennifer’s lab is that if you wanted to collaborate with anyone, you could simply send a cold email, and say, ‘Hey, I’m from Jennifer’s lab’, and they would absolutely respond. So, things that I didn’t have expertise in, I could simply ask ‘is there someone else to collaborate with?’

It’s very impressive that you went straight from doing that to co-founding a company with her. Can you tell me a little bit about that journey?

Early on in my PhD Career, we had been working on more traditional Cas 9 enzymes, and then I formed a really great collaboration with my lab mate, Lucas Harrington, who’s also a co-founder at Mammoth. We had been working very closely, he was focused on discovering a new enzyme, I was more focused on the mechanism and application of those. We’ve always been just amazed that how much there is to uncover with CRISPR. But I think what really sparked our imagination to start a company was the ability to use CRISPR, for detection or diagnostics. This was sort of a new area for CRISPR, we felt there was just no better time to push this forward. So, with Jennifer’s support we decided to just go all in, and we ended up partnering with our colleague from Stanford, Trevor Martin, who’s also the CEO.

It must have been quite a big jump from being a PhD student to suddenly being CTO. How did you manage that?

You just have to accept that there’s so much that you don’t know and you have to constantly learn very quickly. I think part of what was absolutely critical is being able to adapt, be flexible, but also bring in really, really good people. The best way to scale a company is to bring in people who are smarter than you, have done this before, and have much greater expertise in particular areas to help you take these new ideas, and bring them into the company. We also had really fantastic mentors and advisors, not just our investors and our board members, but also scientific advisors, general advisors on the business strategy who really helped us formulate where we could take Mammoth.

How did you find the people management side?

It’s a challenge. Organizations are people and people are human. So we all have our own aspirations and goals. The really fun part is building a team really aligned on a mission. But it also comes with challenges because especially as a new, young manager you’re learning all this in real time. You develop a skill in grad school, and you think ‘this is my expertise, I am in control’, but sometimes when you’re in an organization and managing people, sometimes there’s things outside of your control. There’s other factors at play that you just have never experienced. So, it’s been a learning curve. But it’s also so rewarding to work with people that are just so talented and can move things forward.

What are you trying to achieve at Mammoth?

When we founded the company, we were focused on diagnostics, because again, this was kind of opening up a new world of molecular detection. There’s the incumbent technologies, PCR testing, antigen tests, as well. But really, we felt like there was not a good solution to take really high accurate testing into decentralized environments. And so CRISPR was sort of that new ability to make that possible. But as we’ve been developing the diagnostics piece, we also recognize a core competency of Mammoth was the fact that we had this ability to discover new CRISPR enzymes and that was how this all came about. So we said, ‘Okay, well, as part of building Mammoth into a really great company, we really needed to leverage this whole discovery piece that can basically be the engine for new applications’. Diagnostics is a key focus area. And then as we’ve grown the company, we also been really focused on the therapeutic space. And that’s recently been announced as part of our series D, and also with a partnership with Vertex Pharma to actually develop these new enzymes.

We can’t really talk without mentioning COVID-19. Maybe you could talk a bit about how it impacted the company and how you responded to it?

I still remember, I went to a conference in late December and heard government representatives saying there’s this strange virus in China, we’re still figuring out what’s going to happen, while we were all in person in DC. And then, I came back to San Francisco and it became clear this is a serious situation. I still remember the phone call that I had with Charles Chiu at UCSF. He said, look, this is a growing situation, Charles had some of the first clinical samples from patients infected with COVID. And we said, “okay, we need to be able to demonstrate that there’s a different way we can detect, SARS-CoV-2 in samples.” We felt that our platform was in a really great position to be quickly reconfigured to do that. It was just 10 days from designing the assays to getting the reagents and testing samples, and it was just such a whirlwind at the time. This is before the shutdown. People were still in the lab, I still remember we said, okay, let’s focus this part of the company on COVID. You know, there’s still the other piece of the company on the therapeutic side, we just have to stay the course. It was it was extremely motivating, I think, for us to be able to help.

What do you think have been the key findings in the field of CRISPR, since CRISPR-Cas9 was first discovered?

First of all, I think the clinical trials and the data that’s coming out from things like treating sickle cell disease in patients, I think that’s been remarkable. That’s really what the field is moving towards. And that’s where all these new systems will help enable the other areas since Cas 9, which are new iterations of using CRISPR. Some of the technologies like CRISPRi or CRISPRa, the ability to transiently turn on and off genes, for certain cases is going to be really more critical than permanently cutting or editing that locus. And then there’s also new ways of doing editing like base editing and prime editing, different ways you can modify the genome.

What achievement are you most proud of since you started this journey?

I would say, definitely, the first discovery of using CRISPR for detecting DNA was just one of those once in a lifetime moments. As a scientist, there’s nothing more fulfilling than to say we have this hypothesis, we followed up on it, and then we saw this is a really robust method and tool. That was extraordinarily exciting. And the other thing, too, is navigating all the challenges throughout the pandemic, and being part of a team that’s just so committed to taking these technologies forward. I think that’s been a very proud moment, for me, leading up that part of it.

If you had to give someone who was in your position a couple of years ago some advice, or tips, what would you say?

I would say don’t be afraid to take risks. That was such an important mindset for me. It’s OK to think big, you got to be outside your comfort zone, that I think that’s the kind of message that I think young entrepreneurs should take home.