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Kristen Park Hopson ’01 says mRNA is ushering in a new age of drug discovery and development.
By Amy Martin
oderna’s COVID-19 vaccine was designed in just two days.
Chinese scientists published the genetic sequence of the novel coronavirus on Jan. 11, 2020, and by Jan. 13—more than a week before the first COVID case was documented in the United States—researchers at Moderna and the National Institutes of Health had finalized the sequence for mRNA-1273, the official name of the company’s vaccine.
By late February, when Professors Martha Grossel and E. Carla Parker-Athill led two dozen of their first-year biology students past Moderna’s sleek headquarters in Cambridge, Mass., the first batches of the vaccine had already been sent to NIH scientists in Bethesda, Md.
It would be another two weeks before the World Health Organization declared COVID-19 a global pandemic. On Feb. 28, classes were still meeting in person, restaurants were open, and Grossel and Parker-Athill and their students, having completed a tour of the Koch Institute for Integrative Cancer Research at MIT, walked to lunch to meet one of Grossel’s very first Conn students, Kristen Park Hopson ’01.
Recently named one of Business Insider’s “30 leaders under 40 who are transforming healthcare,” Hopson, who holds a Ph.D. in molecular medicine from Boston University, had spent nearly four years at Moderna leading key cancer research before moving to another Cambridge-based biotech startup, Generate Biomedicines Inc., where she serves as head of medicines.
“There’s something really special about doing research with the goal of making new medicine,” Hopson told the students. “I like the build—taking an idea and seeing if you can make a medicine.”
For years, Hopson and her fellow scientists had been quietly working to revolutionize modern medicine. Then, the pandemic hit.
SOFTWARE FOR THE CELL
Moderna’s vaccine and a similar vaccine developed by the German company BioNTech SE and its U.S. partner, Pfizer Inc., are the very first of their kind. Both use messenger ribonucleic acid, or mRNA, which carries a genetic material (a written message from DNA) that instructs cells to make proteins.
Traditionally, vaccines are made with weakened or inactive pathogens that, when injected, trigger an immune response that can provide protection against the actual pathogens. But the weakened or inactive pathogens have to be cultivated in labs, which can take a significant amount of time—sometimes years.
By contrast, mRNA vaccines don’t include any version of the pathogen itself, but rather instructions for the body on how to make a key protein derived from the pathogen that will trigger an immune response. In the case of COVID-19, the mRNA vaccines instruct the body to make the virus’s distinct “spike” protein. Once the instructions are delivered, the body makes the protein, which triggers the immune system to recognize and react to it.
On its public website, Moderna likens mRNA to “software for the cell.” Normally, mRNA transmits the instructions stored in a person’s own DNA to make the proteins necessary in every living cell. But for decades, scientists have believed mRNA could be synthesized or edited with different instructions to address diseases or pathogens—to tell our cells to make any protein we want.
“Recognizing the broad potential of mRNA science, we set out to create an mRNA technology platform that functions very much like an operating system on a computer,” Moderna explains on its website. “It is designed so that it can plug and play interchangeably with different programs. In our case, the ‘program’ or ‘app’ is our mRNA drug—the unique mRNA sequence that codes for a protein.”
That’s why all Moderna needed to create its COVID-19 vaccine was the virus’s genetic sequence—scientists essentially just needed to plug it in. And if this process can work for one disease, it has the potential to work for almost any disease, from Ebola to Zika, or to treat a range of conditions, including cancer, heart failure and rare genetic diseases.
Moderna alone is working on numerous trials for various vaccines, including cancer and influenza vaccines. And yet, no mRNA vaccine had ever been authorized for use in any capacity by the U.S. Food and Drug Administration—until the Moderna and Pfizer–BioNTech COVID-19 vaccines were authorized for emergency use in December.
“A couple things came together that really allowed for the rapid emergency use authorization, including the advancement of the mRNA technology and the emphasis that BioNTech and Moderna put into building the platforms and harnessing mRNA as a medicine,” Hopson said.
“And it’s a pandemic. That got a lot of folks working at rapid speed to move the development of these medicines at a pace that has not been seen before.”
MEDICINE OF THE FUTURE
In July, The Wall Street Journal asked Moderna CEO Stéphane Bancel what impact a successful mRNA vaccine rollout might have on the future of medicine. “I think the world is going to change tremendously,” he said.
That wasn’t hyperbole. Rapid advances in technology, research and machine learning (a branch of artificial intelligence) have scientists, including Hopson, on the cusp of completely reimagining drug discovery and development and forever changing the way we treat and prevent diseases.
At Moderna, Hopson led preclinical mRNA cancer vaccine research and played a key role in taking the company’s personalized cancer vaccine program from preclinical development into Phase 2 clinical development. At Generate, as the head of medicines, she leads a team of scientists using machine learning and biomedical engineering to create new, more targeted medicines at a much faster pace than was previously possible.
Instead of discovering new medicines through trial and error in the lab, Hopson and her colleagues are using technology to create them.
“In the history of modern medicine, nearly every drug has been discovered or identified from a lengthy, cumbersome and costly process,” Generate co-founder and CEO Avak Kahvejian said.
“Machine learning has evolved to a point where it can unlock the underlying principles of biology. With our proprietary computational platform, we believe we can move from chance drug discovery to intentional drug generation, not only accelerating the development of existing therapeutic modalities but also creating previously impossible ones.”
Generate’s technology allows its scientists to quickly invent new antibodies, peptides, enzymes, receptors and other therapeutic proteins to create new drugs to treat or prevent a wide variety of diseases. These medicines could be delivered with traditional modalities or harness newer and more innovative delivery mechanisms, which might also be developed through generative biology.
The goal, Hopson said, is to get to the point where the structure for a novel drug can be generated instantaneously.
“Traditional drug development is a very expensive and long process. The more quickly you can bring a medicine from concept to approval, the less time and money you are putting into the development process. Lowering the time and cost to make new drugs will inevitably allow the scientific community to bring more new solutions into the world faster,” she said.
“By getting more intelligent about design and research, you can also reduce the number of drugs that fail during development, which also reduces costs.”
Making the process faster, more precise and more cost-effective will allow companies like Generate to create medicines and vaccines for rarer diseases that don’t typically receive the funding to support traditional drug discovery and development. It will even allow them to create personalized medicines unique to a specific individual.
Cancers, for example, are typically treated with a standard protocol of therapies based on the type. Yet, Hopson says, “everyone’s cancer is unique. Sometimes, you need a therapeutic that is individualized for that particular person.”
Cancer cells have DNA mutations that are different from DNA in a person’s healthy cells and are different from patient to patient. Chemotherapy and radiation can kill tumors, but they aren’t targeted for a person’s unique mutations and they damage a lot of healthy tissue in addition to the diseased tissue. Personalized oncology therapeutics could instead teach a patient’s immune system to identify and destroy their particular cancer without harming healthy cells. With numerous trials already underway, these new therapies may soon vastly improve cancer treatments.
“The technology and research advances are allowing us to get much more precise, whether it’s individualized, like cancer, or quickly getting on top of coronavirus or Ebola or other outbreaks and rapidly delivering lifesaving medicine,” Hopson said.
THE COVID-19 SPARK
The COVID-19 pandemic provided the first big test of the advances scientists have been working toward for years—or decades, in the case of mRNA technology.
The scientific community delivered in a big way, Hopson says.
“In less than a year, we went from identifying and sequencing the virus to having emergency authorization for multiple vaccines. We went from having zero ways to detect this virus to being able to buy a testing kit at Costco. We developed antibody treatments, and we have people developing and testing a whole range of therapeutics. I’m so proud of the way the scientific community came together around this virus.”
These developments required a massive influx of private and government funding, increased data sharing among scientists and fast-tracked regulatory processes. Operation Warp Speed, a public–private partnership launched by the U.S. government, also helped facilitate and accelerate the development, manufacturing and distribution of the vaccines, therapeutics and diagnostics.
Now, the challenge will be to keep the momentum.
“We’ve seen how quickly we can move, and hopefully we can take the lessons we’ve learned and carry them over into non-pandemic times,” Hopson said. “I hope the general public’s interest continues in terms of increased funding for research and a more streamlined process for development and approval of medicines.”
For Hopson, it’s an exciting time to be a scientist. And she has no plans to slow down.
“I’ve had the opportunity to work on several oncology clinical trials and see people who are very, very sick have hope in the medicine our company is making,” she said.
“They are putting their faith into what we are doing and taking a chance because they want to live. If they are willing to do that, I can give it my best shot.”