The Humans of the Wyss (HOW) series features members of the Wyss community discussing their work, the influences that shape them as scientists, and their collaborations at the Wyss Institute and beyond.
According to Yang (Claire) Zeng, it’s time for the next generation of vaccine delivery technologies, and she and her team are going to be the ones to introduce a new method to the world. Their DNA origami vaccine platform, DoriVac, will first be applied to cancer. Zeng is incredibly eager to see her work have an impact in the clinic, where she was initially trained as a doctor. Learn more about Claire and her work in this month’s Humans of the Wyss.
What are you working on?
We are developing a DNA origami vaccine platform called DoriVac, which is a newly-selected Wyss Validation Project. There are three components to our vaccine. One is an antigen. Since our first target is cancer, the antigen we’re using is protein fragments from an actual tumor. The second is an adjuvant, or immune response amplifier. Third is the vector, or vaccine delivery particle. In our case, the vector is made of DNA nanomaterials. So, DNA is not being delivered as a therapeutic, but instead forms the building blocks of the vaccine itself.
What real-world problem does this solve?
Existing immunotherapies do not work in up to about 90% of patients, often because elements of a patient’s own immune response are not able to perform their jobs. While therapeutic cancer vaccines have the potential to address this problem by training a patient’s immune cells to recognize and attack the cancer, many have failed in clinical trials.
Unlike other methods, DoriVac uses DNA origami to deliver the antigen and the adjuvant on the same particle, allowing them to work together to create a very strong immune response. Each component has individual benefits as well. On the antigen side, DoriVac can co-deliver multiple highly cancer-specific and patient-specific protein fragments from tumors on the same particle. It makes the therapeutic more specific and immunogenic. The DNA origami structure also allows us to control the precise nanoscale spacing of the adjuvant for optimal activation of the immune cells to destroy cancer and reduce immune-suppressive cells. Plus, it promotes long-term memory to prevent cancer from returning.
There are some other added benefits of our vaccine. It has a strong safety and stability profile. Ten to 100 times less antigen and adjuvant are needed compared to existing medication vaccines. The manufacturing process for DoriVac is low cost and scalable.
We’re currently validating DoriVac for melanoma and colon carcinoma, but we’re also working on lymphoma and ovarian cancer. There is so much potential in this technology. We see DNA origami as the next-generation vaccine delivery method.
The reason DoriVac is so appealing is that it’s already working, and that’s amazing.
What inspired you to get into this field?
I come from a clinical background – I have my M.D. and my Ph.D. I chose not to be a doctor, but my medical training gave me a good understanding of disease. I went into research because I’m driven by the desire to develop something that can be useful for many more patients than I would have been able to treat on my own.
In China, I did research on cell biology and biomaterial engineering. Upon my arrival in the U.S., I studied cancer immunology. When the opportunity came to join Dr. William Shih’s lab and work on DNA nanotechnology, I was excited by the idea of getting into a cutting-edge field where not much work had been done before. I love being able to use my previous knowledge to contribute to this new area.
What continues to motivate and excite you?
The reason DoriVac is so appealing is that it’s already working, and that’s amazing. It can be translated to the clinic and really help patients. I see huge potential in this platform technology – we can target any cancer if we change the antigen. I work a lot every day, but I really feel like it’s exciting work.
The amazing talent that our project has attracted is also very motivating. We have two Ph.D. students, a postdoc, a technician, and an undergraduate student joining us soon. Plus, another postdoc will be joining us in January. What’s also really cool is that we’re an all-female research team currently. We will have several male scientists join us soon.
What are some of the challenges that you face?
How can I spend more time with my family? How can I best utilize my time so I can work on multiple projects simultaneously? Between projects led by students and my own projects, I have about six to seven that are active right now. I’m also writing grant applications, wrapping up manuscripts, looking for independent positions, working with my business partner to translate the DoriVac technology, and doing other work outside the lab.
What do you see as the next steps in your career?
When we spoke with investors during the Nucleate program, they saw big potential in DoriVac. I know it will be helpful to patients once it gets to the clinic, and I’m confident that it can get there. I’d like to remain part of the team once the technology spins out of the Wyss. My experience with DoriVac has made me even more committed to translational research. I’m also excited to run my own, independent lab as a faculty member to bring my other scientific ideas to life.
What is unique about the Wyss?
There is a translational focus here that’s very inspiring. There’s so much talent concentrated at the Wyss, and everyone has that mindset, which makes the research more exciting. Every part of the organization feels like it is put in place to help your technology get to the real world.
There’s so much talent concentrated at the Wyss, and everyone has that translation mindset, which makes the research more exciting. Every part of the organization feels like it is put in place to help your technology get to the real world.
The resources available at the Wyss make my life, and DoriVac’s path to commercialization, much easier and more efficient. For example, Amanda Graveline and the veterinary team have been tremendously helpful with our animal studies and the labs are well managed by people like Mike Carr and Maurice Pérez. Thomas Ferrante and Eric Zigon have been very helpful with the important facilities we use at Wyss such as the microscopes and flow cytometer. Ally Chang and Vani Velamoor help us with the business development and legal side of our project. Plus, Lei Jin and Benjamin Boettner from the communications team are helping us to create an animation explaining the technology.
How do you collaborate with teams across the Wyss Institute?
I always reach out when I need help, and if I do collaborate on a project, I always ensure that people’s efforts are recognized, their names appear on authorship, and we apply for grants together. All these things are important for establishing and continuing collaborations.
We have a few research collaborations within the Wyss. At the beginning of the project, I read a lot of Dave Mooney’s work on how he used biomaterials to do immunology-related research. It was so inspiring and impressive. I spoke to William about working with Dave, and we set up the collaboration.
We also work with members of Don Ingber’s lab. That came about more informally, through a discussion with a friend who was on the team led by Girija Goyal. We found each other’s work interesting, so we came up with the idea of collaborating and trying out some experiments. Later we applied for a grant together to work on an infectious disease vaccine.
How have your previous experiences shaped your approach to your work today?
Translational research attracted me because of the high level of innovation and the idea that we can develop something that might change the world.
My professional background and my personality have had the biggest impact on my approach. During my Ph.D., I initially thought I’d enter industry or focus more on teaching than research. However, translational research attracted me because of the high level of innovation and the idea that we can develop something that might change the world. Plus, during the year I spent shadowing doctors in the hospital, I observed disease up close and saw how desperate people are for new treatments.
In terms of my personality, I’m very detail oriented. I learn new things fast. I look at an experiment and quickly figure out what the problem is and fix it. I also have broad research experience; I can easily design different experiments to answer scientific questions. So, I’ve had a high rate of success in my work, which has given me the confidence to continue.
What do you like to do outside of work?
I like to spend time with my kids and my husband – I have two boys, one is twelve and the other will be four very soon. We go camping, hiking, and fruit picking a lot in the summer. We enjoy the beach too. Boston winters are long, but we also enjoy the snow for skiing or snowball fights. It is also fun to watch my older son in his Taekwondo competitions.
My husband is a lawyer who works from home. While he is also busy, he takes care of most of the housework, such as sending the kids to school and cooking. I like to work with him in the kitchen if I can. I enjoy cleaning and improving the home decoration if I have time.
What is something fun about you that someone wouldn’t know from your resume?
I like to sing and dance. I participated in a Latin dance program during my postdoc in China and we were on TV once. I was also the coach for the girls gymnastics team while I was in medical school. However, between my work and my kids, I don’t have much time to do this anymore. Now I just do some workout dance to keep myself fit.
If you had to choose an entirely different career path, what would it be?
Maybe I would be a doctor. I’m more of a people person, so I think I’d be good at that. I initially chose not to be a doctor because I thought I wouldn’t have enough time for my family. But now I’m so dedicated to my research that it seems almost funny that I thought medicine would be so different!
What does it feel like to be working on cutting-edge technology that has the potential to have a real and significant impact on people’s lives and society?
If our technology can cure cancer patients, that will be incredible. That’s huge! We also recently raised this ambitious concept that DNA origami could be the next generation of delivery vehicles for all kinds of drugs, replacing lipid nanoparticles, because of its many advantages. The huge potential of DNA origami to have a very significant impact is extremely exciting.