At the Forefront of Gene Editing

Inspirational Instructor Dr. Geoff Sargent brings bleeding-edge gene technology to classes

I asked Geoff his thoughts on being named a 2020 Inspirational Instructor. He looked around his garage—where he was taking our interview on Zoom, 2020 being what it is—seemingly trying to come up with how to answer.

He looked back at the screen, cocked his head and laughed! Not the response I was expecting. Instead, he replied, “I'm embarrassed to say I haven't really thought about it a lot. Everything's so busy. I'm juggling all these courses. It's wonderful, and it's an honor. But I've got too much to think about.”

No truer words had been spoken.

When I last caught up with Geoff in 2016, he had just founded biotech startup GeneTech, which focuses on improving the accuracy of CRISPR/Cas proteins, TALENS and Zinc Fingers and reducing some of their mutagenic effects. The company has made great headway, resulting in a patent filing nearly 18 months ago.

As one could imagine, propelling GeneTech to be a competitive market-player takes most of his time. But his passion for teaching remains strong and he continues to teach with us and at other schools. In fact, he’s instructing three classes: Introductory Biochemistry, and upcoming Stem Cell Biology, Research and Discovery and Biochemistry live online classes.

Oh, and he also volunteers his time with counseling and sits on the board of directors for the California Bluegrass Association. In fact, when we chatted, he was trying to figure out if it was feasible to live-stream their annual Bluegrass Festival.

So it should come as no surprise that he hasn’t had much time to think about being named an Inspirational Instructor this year.



I came up with a way to make CRISPR/Cas9 gene editing significantly more efficient because of my particular background of studying DNA damage.



So let’s start by talking about GeneTech. Tell me more about the company.

It's a CRISPR startup, but what we're trying to do is improve the efficiency of the Cas9 because the efficiency of the technology is currently low. Efficiency in this sense means how many edits are actually made versus the maximum number that theoretically could have been made. That is a limiting issue for the widespread use of CRISPR/Cas9 right now. The technologies that are being used break DNA where you tell it to. And so you can program in the address, and then it goes and breaks the DNA at that address. That makes it easier to fix changes around the break.

If you wanted to pick sickle cell anemia, you send your Cas9 to make a DNA break near where that mutation is, which makes it easier to fix the mutation. What we're trying to do is improve the efficiency because the efficiency—from cell to cell, from gene to gene—varies a lot.

I came up with a way to make CRISPR/Cas9 gene editing significantly more efficient because of my particular background of studying DNA damage. We wrote a patent applicant around the idea and I was able to get some research done to support the claims in the applicant. We've had some early indications that the patent application is going to be reviewed favorably.

If the patent gets issued earlier rather than later, then it's a lot easier to raise money. And then you have an issued patent in your pocket that you can go to other companies and say, “We've got this great technology. It's going to make your life better. We'll license it to you, and you can raise money through licensing fees and other things.” To get a patent allowed in the CRISPR space would be huge.



I got into this research about 40 years ago because I wanted to treat genetic disease.



As the general public, are we starting to understand how much CRISPR will change our lives?

The world does not understand how much this is going to change us. You just can't say how important and how much potential this has. It's mind-boggling.

I got into this research about 40 years ago because I wanted to treat genetic disease. And I knew that for a lot of genetic diseases, the only way you can treat them is treating the eggs and sperm. That's still what I want to do once the ethical considerations have been sorted out.

But that same technology—if you make it good enough—allows scientists to go in and edit any gene. It would allow you to make changes for your child to be a better football player or a better dancer. That's the ethical dilemma that we're going to have. How do we police it? There's going to be the prospect of others doing it unregulated.

I think we're going to be confronted with having to make the decision in the range of five to 10 years.

I’ll use sickle cell as an example. We'd love to be able to go in and fix the mutation that causes it. But that “fixing the gene” process is still unpredictable enough that it's not ready for clinical trials. We need to make it more predictable, less damaging off-target before we can take it into the clinic.

So while you’re spending hours upon hours making the technology more reliable, you’re also spending considerable time outside of the lab. The last time we spoke you were volunteering at a crisis hotline.

Yes, though I've been taking a break. I've got two dogs and my wife. The noise issue—I can't imagine being on a really intense call and having all this racket going on. So I've stepped back from it for a period of time. I still volunteer with them on some other things. Eventually when they open the brick-and-mortar call center, I'll go back.

I started on the crisis line because at one point I was thinking about retraining into genetic counseling.

Genetic counseling?

It's actually been around for a while, and interestingly there used to be a Genetic Counseling degree offered through UC Berkeley. Originally, it was to counsel women who were dealing with either their own inherited cancer issues or for pregnancies that might involve fetuses that are going to have some inherited genetic problems.

So it's a mixture of both genetics and understanding the genetic disease. And then the counseling aspect is trying to help the clients answer questions such as “Do I get tested further? Do my family members get tested for genetic disease?” Because now if you have a genetic disease and you know there's a chance your kids have it, then you might need some help in making a decision on whether they get tested.

So there's all those issues around trying to educate clients on the real risk. What's the practical, day-to-day risk, and what do you do about it?

It involves talking to the patients about how to deal with their genetic disease, how to manage it, how to notify their family members.

But the graduate programs to get certified for this are very competitive. And this was at the time my biotech startup came together. I had a fundamental decision to make: Which path do I take? So I went ahead and took the startup path.



What I try to do in all my classes is have the students engage. It's not always easy.



How have you adapted to your classes to fully online learning?

What I try to do in all my classes is have the students engage. It's not always easy.

What I really want to do is restructure each lecture to take advantage of the online opportunity. I haven't quite cracked the nut on what does that structure look like? It's forcing me to rethink how I want to structure the classes and focus more on what's important. There's so much material in the biochem course that it's hard for me to put some of it aside in order to make time for more in-person discussion.

Has the makeup of your students changed over the years?

It's a mix. For the biochem course, the students were history majors who later decided to pursue medical school. So they've been out of school for a few years.

But most of them haven't had a definitive career. They'll have been research associates in labs or clinical trial managers or be associated with clinical trial management in various departments. And now they're taking science courses to make them competitive for medical school.

Then I have a few students who have been in the workforce for four, five or six years. And oftentimes, they do have a bit of a hill to get over in order to get back in the study groove. I had a guy who was working as a BMW tech and was looking to get into dental school. He drove up from Monterey once a week to take my biochem course. Here's a guy, laying it all out there to go to dental school, and he's got a family and a job. These students are amazing. I have a lot of respect for those who come through later in life to change their path—I just love that.

And that’s why you’re a 2020 Inspirational Instructor—congrats from all of us!