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.
Sayo Eweje loves finding solutions, whether he’s looking at a Rubik’s Cube or a technical challenge in the lab. When faced with the problem of how to impact patients at both a personal and population level, he found the answer in an M.D./Ph.D. program, where he is training to be a medical doctor while further developing his scientific research mind. The next problem: treating genetic disorders like cystic fibrosis and sickle cell anemia. At the Wyss, he is working to solve this using a protein nanoparticle delivery system that transports gene editors to the right cells in the body, so they can directly correct mutations. Learn more about Sayo and his work in this month’s Humans of the Wyss.
What are you working on?
I am working on a protein nanoparticle delivery system to transport gene editors to their intended target sites in the body. We’ve been working on this self-assembling human protein material, derived from the protein elastin. We can engineer a protein polymer version that assembles into the nanoparticles we use to encapsulate and deliver mRNA and proteins. This delivery mechanism would allow us to treat diseases by transporting gene editors to the right cells in the body to directly correct the mutation underlying a disease or create a change in the genome that would indirectly address the issues a patient is having.
Gene editors are susceptible to degradation by proteases, enzymes that can break down proteins, or nucleases, enzymes that can cut nucleic acids. These gene editors cannot passively enter cells. So, we need this delivery mechanism to protect them and help them bypass the cell membrane and get directly to the nucleus, where they can make their edits.
What real-world problem does this solve?
We’re trying to use our delivery mechanism to treat inherited disorders. One area we’re focusing on, as part of the ENTER Validation Project, is lung diseases like cystic fibrosis (CF). CF is caused by a mutation in a chloride channel that reduces its activity. Patients end up with mucus in their lungs and other organs, making them susceptible to infection. Some patients do not respond to existing small molecule drugs, so gene therapy is their best option. We aim to use our vehicle to deliver gene editors into epithelial cells, which line the lungs, to fix the mutation and restore normal cell function.
We’re also focusing on using our technology to treat inherited blood disorders, such as sickle cell anemia. A therapy was just approved that involves editing hematopoietic stem cells (HSCs) outside the body to create a change in the genome that results in the expression of healthy hemoglobin. This is exciting, but there are challenges with this approach. For example, patients need to undergo chemotherapy to clear their bone marrow and allow the edited cells to engraft. There are also logistical complexities involved in extracting the cells from patients, shipping them to an off-site location for editing, and safely shipping them back. Our goal is to create a vehicle that would allow us to do all of this within the body, so patients won’t need chemo, and cells won’t have to be transported.
What inspired you to get into this field?
I am a student at the Harvard-MIT Health Sciences and Technology M.D./Ph.D. program, where I study Medical Engineering and Medical Physics. This type of combined degree appealed to me because of the opportunity for two levels of patient impact. There’s value in the direct patient-physician relationship, and as a doctor, I could shepherd a patient through their medical journey, acting as a valuable resource for them. Leveraging my knowledge to fundamentally change someone’s life for the better will come with a lot of responsibility, but also a lot of joy. However, I realized that without research training, it will be challenging to think about the bigger picture. It’s through science that we have an opportunity to create solutions that could impact people on a larger scale.
While I was an undergraduate, I worked in Kit Parker’s lab. That was my first foray into bioengineering research. There, I developed a scientific mind and an interest in using materials to engineer new solutions for treating diseases.
It’s through science that we have an opportunity to create solutions that could impact people on a larger scale.
I began graduate school around the time the COVID-19 pandemic started. There was a renewed interest in genetic medicines and mRNA. As I was deciding which faculty member to work with, an opportunity arose in Elliot Chaikof’s lab to work on developing protein nanoparticles for gene editing, specifically in HSCs. I knew what a huge challenge it was to reach these cells, and what a huge impact overcoming those difficulties would have. The promise of the work motivated me to dedicate time to solving this problem.
What continues to motivate you?
Thinking about the person at the end of the journey – the patient. As a clinician, I will have a duty to my patients to help them understand and overcome their diseases, and that responsibility motivates me to be as good as I can be. On the research side, I love trying to solve significant problems, but I also keep in mind that there’s a bigger picture. Solving a challenge in the lab enables us to impact patients positively.
What excites you the most about your work?
There’s a design, build, and test cycle that’s inherent to all of engineering. For example, we had a hypothesis that incorporating certain proteins onto the surface of our particles would improve uptake into the cell types we’re interested in. What’s exciting is that we get to conceptualize the design, see how it fares, and then make adjustments and continue going through the iterative improvement process.
What are some of the challenges that you face?
There’s not much of a precedent for what we’re doing. When we develop a new protein nanoparticle design, we can take inspiration from previous literature, but there is a lot that we have to figure out on our own. It’s a challenge, but we learn from one another and from others in the field.
How did your work become a Validation Project?
Our Validation Project came about serendipitously. I was getting coffee, and I started talking to Ken Carlson about our work. He mentioned that he was interested in infectious diseases and how to deliver drugs to the lungs better. One thing led to another, and he became the Advanced Technology Team member on our Validation Project proposal.
What is unique about the Wyss, and how has that impacted your work?
The Wyss presents opportunities for these random collisions, like the one I had with Ken. I have so many friends and colleagues here, and it’s a great space for connecting with other researchers on a personal and intellectual level.
The Wyss provides a breadth and depth of resources that facilitate great science, but also emphasizes technology translation. This interests me because commercialization is a necessary step on the path to getting our work from bench to bedside.
The Wyss provides a breadth and depth of resources that facilitate great science, but also emphasizes technology translation. This interests me because commercialization is a necessary step on the path to getting our work from bench to bedside. I have colleagues dedicated to figuring out how to get our work to patients and helping us researchers to keep that perspective in mind.
How do you collaborate with and receive support from teams across the Wyss Institute?
In terms of collaboration, my team has been working with members of George Church’s lab to look at gene editor variants that could improve the specificity of the edits we’re trying to install.
On the Business Development side, Bill Bedell has been instrumental in connecting us with the Cystic Fibrosis Foundation. That organization is helping us obtain patient cells to work with, which is crucial for our research.
How have your previous work or personal experiences shaped your approach to your work today?
Over the years, I’ve conducted experiments examining the delivery of therapeutics to various sites, including the eye, ear, lungs, and bone marrow. This prevents me from thinking about things in a silo and keeps me open to several potential applications. At the same time, I can still focus on the direction that is most promising or meaningful. This allows me to think broadly about new ideas while also staying focused on the key challenges we face.
What do you like to do outside of work?
1/3 Sayo enjoys birding in his spare time. Credit: Sayo Eweje 
2/3 Sayo took this photo of two Baltimore orioles fighting mid-air. Credit: Sayo Eweje 
3/3 This is one of Sayo's favorIte birds, the gray catbird. It has a remarkable and funny cat-sounding call. Credit: Sayo Eweje
My hobbies change over time, but the most persistent thing is basketball, both watching and playing. I grew up in North Carolina, so we watched a lot of Duke and UNC games. I’ve also gotten into birding recently, just going to local parks and trying to catch some wildlife. I also enjoy watching TV – I’ve been watching “The Pitt” lately as I transition back to medical school.
What is something unique about you that someone wouldn’t know from your resume?
My go-to fun fact is that I have an identical twin brother. He’s in Philadelphia right now, about to start his residency. I also went through a phase where I was speed-solving Rubik’s Cubes. I can still solve them pretty quickly.
If you had to choose an entirely different career path, what would it be?
I have an interest in teaching. Growing up, my parents did a lot to put us in a good position and emphasized the importance of learning. My education largely drove the opportunities I’ve had. I am passionate about trying to pay that forward and inspire the next generation. Teaching is a meaningful way to do 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 daunting but exciting. It’s daunting in the sense that as you deal with the day-to-day struggles in the lab, it can feel deflating. But it’s exciting because, as I pour so much time into my work, I know it can have a meaningful impact. So, I try to keep that bigger picture in mind and see the forest instead of focusing on the individual trees of the day.