By Sonia K. González, DrPH, MPH

Dr. Premsrirut was an MD/PhD Medical Scientist fellow at the SUNY Stony Brook School of Medicine and Cold Spring Harbor Laboratory, where she received extensive training in the fields of medicine, trauma surgery, cancer genetics, and molecular biology. Her research at Cold Spring Harbor Laboratory in the lab of Dr. Scott Lowe specifically focused on determining the role of tumor suppressor genes in tumor maintenance of lung adenocarcinoma, in which she developed a speedy platform for the generation of cancer mouse models – research that laid the groundwork upon which Mirimus was founded. She received a B.A. in Molecular Cell Biology and Biochemistry from UC Berkeley. She was a Goldman Sachs 10,000 Small Businesses Scholar in Entrepreneurship and Babson College. Dr. Premsrirut is also currently an Assistant Research Professor of SUNY Downstate Medical School.

Can you discuss your background and how you became interested in genome editing technologies? Tell us the story of how this led you to Mirimus?

I received a BA in Molecular Cell Biology from UC Berkeley and an MD/PhD in Genetics and Cancer Biology from SUNY Stony Brook School of Medicine and Cold Spring Harbor Laboratory. My interest in genome editing came from my PhD thesis research which utilized mouse models to study the role of tumor suppressor genes on tumor pathogenesis. Our ability to genetically manipulate embryonic stem cells and generate live animals directly from the engineered stem cells completely fascinated me. We were able to create tumors de novo, which allowed us to dissect the intricate genetic pathways involved with cancer progression. It was through this research and the difficulties I encountered in engineering animals that lead us to meddle with new technologies to manipulate gene expression. At that time, Cold Spring Harbor Laboratory investigators were at the forefront of uncovering the machinery involved in the RNA interference pathway and learning how to hijack this pathway to silence any gene of interest. We thought if we could get this to work reproducibly in animals, this would change our ability to study genes. We could not only turn genes off, but because we were not disrupting the DNA itself, the gene silencing mechanism was reversible, much like therapeutic inhibition. It was toward the tail end of my PhD research, after much trial and error, that I was able to build an efficient and highly reproducible platform to engineer RNAi mouse models. We had a platform to seamless engineer mice where we could model drug inhibition genetically, without the actual drug. And we believed this would be a powerful tool for research. That is when we pitched the idea to VCs and received funding to set up the company.

How would you describe your technology to the layperson? What is it? How does it work?

RNA interference (RNAi) originated in organisms as a viral defense mechanism. The mere exposure to viral RNAs would trigger specific enzymes in this pathway to chop up the RNA and prevent viral protein expression. Over time, this pathway evolved and is now used to modulate our own gene expression. By studying the details of how this pathway works, we now know how to hijack it and force it to inhibit specific genes of interest that we wish to study. For example, we can deliver small synthetic RNAs that look like viral RNAs and trigger this pathway to turn off specific genes. By engineering animals to harbor these small RNAs, we can control the expression of any gene of interest.

How long did it take to make the idea for Mirimus into reality? How is the new genome editing tech changing the field of healthcare?

We were engineering animals using this specific RNAi pipeline for almost 2 years before we received funding from the National Cancer Institute to generate 1500 models. It was through this funding that we set up the pipeline and laid the groundwork for what would become Mirimus in 2010, which was formed on the premise of RNAi technologies. Only two years later, the Doudna and Zhang laboratories published their groundbreaking work based on CRISPR/Cas9 genome editing technologies, which would change the way we engineer animals forever. Because of this technology breakthrough, we have had to continuously reshape our vision and become experts in new areas in order to remain at the forefront of genome engineering. Our ability to cut and paste DNA using these novels technologies is unprecedented and has made its way into the clinics in just a few short years. There is no doubt that it will change healthcare through its use in so many applications in biomedical research and in the clinic, where there are thousands of monogenic diseases that could be treated.

What has been the hardest part about transitioning from being in a researcher into the business world?

The most difficult part of the transition was learning that not all good ideas have commercial potential. The ability to scale cost-effectively and execute an operational pipeline is the key to commercialization, and having the right people to do so is the most critical component of any successful business. If you need a PhD level scientist at every step of the process, you will not be able to execute cost-effectively. Managing people and sharing your visions and expectations is crucial to building cohesive streamlined operations.

Why NYC?  Why do you think it’s becoming a leader in the health-tech sector?

After spending a decade in NYC and establishing my foundations here, it was hard to leave. My founding institution was also NY-based, so we chose to remain close to home. NYC is at the epicenter of a biotech boom because many people are naturally drawn to the vibrancy of this city. It brings together more cultures than any other city in the world and people from so many industries as well. We have some of the best medical institutions here and that draws in the talent. We have the financial district here so keep a close watch on the research and be involved early on in the process. We have culture, arts, music, something for everyone to enjoy. That is what makes NYC so special and that is what keeps me here. NYC still has a long way to go to catch up to Cambridge, the Bay Area, and San Diego, but the people here, no matter what industry, have always seemed to have the drive and that “fire in their belly” to make it happen.

What do you believe to be the greatest challenges for health-tech? And the greatest opportunities?  How do you think technology can help?

A great challenge for health-tech in the future, particularly in the genome editing space, will be the moral and ethical challenges we will face as a scientist. This technology gives us enormous power to shape life on this planet and how we will do it responsibly as a community will be an enormous challenge. Already we saw the CRISPR babies and the backlash from the scientific community across the globe, and yet this may not be enough to stop others from doing the same in the future. In agriculture, we have the ability to engineer resistant foods that can endure droughts and survive antimicrobial epidemics; these crops may enable us to feed the globe and prevent hunger anywhere. But we have to do this responsibly, as we cannot always foresee the impact of engineering until many years in the future.

How can health tech help marginalized communities? Do you see health-tech and public health working more closely in the future to solve some of the issues in disadvantaged communities?

I believe health tech can make access to health care much easier, enabling marginalized communities access to experts through mobile devices, video chat, and diagnostics. Growing up, I could never foresee that we would be able to walk around with our cell phone devices that are mini-computers and can send messages to anyone in the world in an instant. The clarity of calls and videos can shape the way patients can be seen by experts from anywhere in the world.

Another fascinating development is how routine DNA sequencing has become. The cost is now only a tiny fraction of what it was 20 years ago, giving us the ability to see into our genomes and unravel their complexities. With decreased cost, access will become more affordable and this will certainly help our disadvantaged communities.

What is the best advice you have been given?

Always be present in the moment. Learn from the past and then leave it in the past where it belongs so your future can be open to many opportunities.

FACT SHEET

• Grew up in: Born in Montgomery, AL. Grew up in Las Vegas, NV. My mother was a pediatrician in the Air Force so we were stationed at Las Vegas Nellis Air Force Base
• City or town you call home: New York is now my home, but Las Vegas will always be on my list as well
• Current location: Long Island City, NY
• Job title: President/CEO
• Background and education: BA – UC Berkeley; MD/PhD – SUNY Stony Brook & Cold Spring Harbor Laboratory
• Your motto: Work hard, play hard
• As a child you wanted to be: a chef