The Humans of the Wyss (HOW) series features members of the Wyss community discussing their work, the influences that shape them as professionals, and their collaborations at the Wyss Institute and beyond.
Anastasia Ershova loves fencing because every opponent is a new puzzle to solve, and both fencers are constantly engaged, making adjustments based on each other’s actions. The same could be said for her work designing and building novel nucleic acid nanostructures. There is a fast iteration cycle from idea to result, and then she can make adjustments based on experimental outcomes before trying again. At the Wyss, Ershova is a Scientist developing and fabricating nanostructures from DNA and RNA for use in therapeutics and diagnostics. Learn more about Anastasia and her work in this month’s Humans of the Wyss.
What are you working on?
I’m working on a number of projects, all involving designing and building novel nucleic acid nanostructures for therapeutic and diagnostic applications. For example, I’m working on the ARPA-H DAIRS project, where I am developing duplex RNA nanostructures to safely and effectively activate the innate immune system to fight cancer. This is a highly multidisciplinary project, involving researchers from the teams of Don Ingber, Natalie Artzi, and William Shih, which is where I’m from.
At the same time, I’m advancing the work I did during my Ph.D., called Crisscross Nanoseed Detection, which is an enzyme-free technology driven by DNA self-assembly that can target specific nucleic acid sequences and proteins for diagnostic applications. We hope this approach will enable us to diagnose diseases more quickly, accurately, and cost-effectively than we currently can.
What real-world problems do these projects solve?
Cancer has remained an intractable disease in large part due to its ability to evade the body’s defenses. The innate immune system is the body’s first line of defense. It has evolved to go into full gear in response to foreign nucleic acids, like viral RNA and DNA, triggering the production of signaling molecules that have antiviral and anticancer efficacy by promoting immunity and suppressing tumor growth. However, most therapeutic approaches explored to date harnessing the innate immune system have suffered from dose-limiting toxicities. We believe we can use duplex RNA nanostructures to achieve lower systemic toxicity and, consequently, wider therapeutic windows.
The sensitivity of the detection of biomarkers, like proteins, is commonly limited by the background rate of false positives and often requires complex instrumentation that is inaccessible in a point-of-care setting. Crisscross is a new way of detecting biomarkers down to the single-molecule level by using them directly to trigger the formation of “nanoseeds.” The nanoseeds then initiate downstream signal amplification via the rapid, isothermal self-assembly of much larger, ribbon-like DNA structures. We are actively working on expanding this principle to exponentially amplify DNA structures to make detection as fast and low-cost as possible.
What inspired you to get into this field?
I’ve always been driven by bringing together approaches from a broad range of fields to solve biomedical problems. When I started my Ph.D., I was more interested in regenerative biology from a biophysics and bioengineering perspective, and had a great first rotation in an axolotl limb regeneration lab. Then I met William Shih at a departmental retreat. I thought his research sounded almost like science fiction, so I decided to do a rotation in his lab next. The work felt like solving puzzles all day and I was hooked.
What continues to motivate you?
The cool thing about DNA nanotechnology is that it’s so interdisciplinary, and there is always more to learn. It feels like I’m developing an unusual constellation of knowledge that enables me to do something truly unique and hopefully impactful. That’s very motivating.
What excites you the most about your work?
I work across all levels of abstraction, from designing complex, self-assembling systems akin to molecular Lego, to optimizing them computationally, to fabricating them in the lab, and then testing whether they are effective for a given application. It’s a fast iteration cycle from idea to result. I find it satisfying to work that quickly and keep adjusting until I get it right.
Biology is complicated, and many of the unmet needs in medicine stem from that complexity – it’s exciting to me that our field might provide the tools to unlock solutions to some of these problems.
The idea of making an impact is also inspiring. Biology is complicated, and many of the unmet needs in medicine stem from that complexity – it’s exciting to me that our field might provide the tools to unlock solutions to some of these problems.
What are some of the challenges that you face?
The complexity of biology and self-assembly is exciting, but it’s also where the challenges come in. Sometimes, if a design doesn’t work, it can be difficult to pinpoint exactly why, and it is often easier to move on to the next design iteration.
Why did you want to work at the Wyss?
The Wyss embodies everything that drives me to pursue science. There is a focus on highly interdisciplinary engineering work, with an emphasis on making a positive impact on patients.
I joined the Wyss as a Ph.D. student in 2019 and became a Staff Scientist two years ago. This may sound cliché, but the Wyss embodies everything that drives me to pursue science. There is a focus on highly interdisciplinary engineering work, with an emphasis on making a positive impact on patients. Even the term biologically inspired engineering resonated with me, because biology has come up with clever solutions to many problems. Therefore, if we want to achieve the same, it’s great to learn from that.
What is unique about the Wyss? How has that impacted your work?
The whole mindset and framework of thinking about impact, and considering the path you will need to take to reach patients from a project’s conception, is unique. We’re not just doing science for the sake of science or publications; we’re thinking through how our work can be translated into the real world. Now, every time I come up with a new idea or project, even if it seems high-risk or esoteric, I consider what steps would be needed to give it the best chance of making a meaningful impact.
It’s also a highly collaborative environment. A lot of my work requires interdisciplinary expertise, so having access to such a variety of people is essential. Plus, the whole innovation pipeline, including the Validation and Institute projects, is a great catalyst for impact. I became a scientist because I want to make a difference, and the Wyss is the perfect place for that.
How do you collaborate with other teams across the Wyss Institute?
The ARPA-H DAIRS project is a prime example of collaboration at the Wyss. With his extensive industry experience, Ken Carlson has been keeping us on track to develop our RNA nanostructures into clinically viable therapeutics. For this, we need to develop potent structural and sequence designs, optimize an effective delivery formulation, assess safety and efficacy in clinically relevant models, and have a way of producing the therapeutic sustainably at scale. To address these challenges, our big interdisciplinary team draws on the delivery mechanisms expertise of the Artzi lab, the Organ Chip experience of the Ingber lab, the Shih lab’s knowledge of nucleic acid nanostructures, and Wyss spinout EnPlusOne’s specialty in enzymatic RNA production. The project works like a well-oiled machine: for example, I’ll hand over the nanostructures I designed to Sylvie Bernier and the Ingber team to test in vitro, and the Artzi team will then take our top candidates in vivo. More generally, it’s also been fantastic to collaborate with members of the Shih lab on projects like Crisscross – it’s truly a team effort.
How have your previous work and personal experiences shaped your approach to your work today?
During my undergraduate studies at Cambridge and through various research projects, I’ve been fortunate to explore different scientific disciplines and form connections between areas like pharmacology and materials science. A data science internship at Unipart Digital gave me a firsthand glimpse into how quickly insights from code can reach the production floor. Participating in entrepreneurial programs like Activate Bio and Fifty Years – 5050 introduced me to tools that can help move discoveries beyond the lab. These experiences have given me a sense of urgency and made me more comfortable with drawing on approaches outside of my domain.
What do you like to do outside of work?
Every six months or so, I seem to acquire a new hobby or skill. For example, recently I’ve taken on climbing, juggling, and stop-motion animation. One thing that has really stuck is fencing. Three years ago, given the weather in Boston, I was looking for an indoor individual sport, so I decided to try fencing, and I loved it. It’s been described as physical chess. Every opponent thinks and moves differently, so it’s almost like each one is a new, constantly adapting problem to crack. Tournaments have also given me a great excuse to travel and see more of the United States.
What’s something unique about you that someone wouldn’t know from your resume?
I grew up with three native languages. My parents are Russian, but I was born and grew up in Greece, where I went to a British school. Many of my teachers were from the U.S. and Canada, so combined with doing undergrad in the U.K. and now having lived in the States for a few years, my accent has ping-ponged between British and American my whole life.
If you had to choose an entirely different career path, what would it be?
Probably an aerospace engineer. It boggles my mind what humanity has achieved in that area. My grandfather actually earned a stack of patents for sheet-metal techniques that shaved precious weight off airframes. Still, I figured my odds of making a dent in biomedical research were higher than my chances of hitching a ride to orbit, so I stayed Earth-bound and ran with that.
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?
It’s incredibly motivating. I cannot imagine doing anything else.