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Isaac Han on AAV Gene Therapy

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. 

Isaac Han always liked building things. When he was a kid, he built with Legos, but now he builds gene therapy vectors with AAV. His team hopes to use this method to develop an HIV prophylactic to prevent the disease in regions where it is endemic. Learn more about Isaac and his work in this Humans of the Wyss.

What are you working on?

I’m working on a skin immunoprophylaxis project funded by the Bill and Melinda Gates Foundation. Essentially, we’re trying to use recombinant AAV, also known as adeno-associated virus, as a gene therapy vector.  Gene therapy is the delivery of genetic material to your body’s cells to achieve a therapeutic effect. We’re trying to use that method to develop a potential HIV prophylactic.

What real-world problem does this solve?

HIV is endemic to certain regions where access to medications and treatments can be difficult. A lot of work has been done trying to develop a vaccine, but that’s proven very challenging. This is because the traditional method of vaccination – stimulating your body’s natural immune system response to produce antibodies against an antigen – has proven ineffective for HIV. One way we are trying to leverage gene therapy technology with AAV is to try and make cells in your body produce this antibody directly. This involves taking a gene that codes for an HIV-neutralizing antibody, putting that into a viral vector, and delivering it to the skin. Cells in the skin will then produce this antibody, which will enter systemic circulation, and confer resistance to HIV.

What inspired you to get into this field?

I used to do basic biology research, and with that there’s so much unknown that I felt as if I were drowning in unanswered questions. In basic biology there are often more questions every day than there are answers. Some people thrive off of that, but I’ve discovered that it’s important for me to be able to achieve tangible results on a shorter timescale.

I also enjoy building things. Whether it’s physical things, like Lego structures when I was a little kid, or relationships with people while building and developing a team.

A yearning for answers and a desire to construct something guided my interest more towards engineering and the specific technologies I’m helping to develop right now. With my current project, I’m producing something tangible every week.

 What continues to motivate you?

The work I do has broader implications beyond the scope of the project I am working on because gene therapy is coming. It’s growing, and it’s really cool to be a part of this paradigm shift.

Isaac Han

I’m motivated by the fact that what I am working on is more of a platform technology and tool as opposed to a very specific invention, which means it may lead to huge impacts beyond what anyone is thinking of today. I am part of something that has potential to change the world. Though this skin immunoprophalaxis is very specific, all of the techniques I’m using, all of the experiments I’m doing, are easy to pivot to other applications. This can radically redefine what we view as therapeutic, and that’s incredible. I am very lucky in that I genuinely enjoy what I do, but it’s also useful. I like the fact that I am on the cutting-edge of technology at the Wyss Institute and in the Church lab. The work I do has broader implications beyond the scope of the project I am working on because gene therapy is coming. It’s growing, and it’s really cool to be a part of this paradigm shift.

What excites you most about your work?

The potential to change how people perceive medicine. I enjoy telling people that I make virus that could one day be used to treat other viruses. But it’s not just HIV and it’s not just AAV. Gene therapy is a huge field that opens the door for so many things. It has the potential to treat diseases that were previously untreatable.

However even with the incredibly interesting science I work with, at the end of the day what really keeps me excited are the relationships with the people I work with and how well the group communicates. I love being in such a dynamic workplace environment. There are moments I’ve witnessed where innovative ideas form because someone with a completely different scientific field of expertise overheard a conversation in the bay over. I find that really stimulating and exciting. Being at the Wyss Institute has given me opportunities to collaborate and grow that I would not have had elsewhere.

There are moments I’ve witnessed where innovative ideas form because someone with a completely different scientific field of expertise overheard a conversation in the bay over. I find that really stimulating and exciting.

Isaac Han

What are some of the challenges that you face?

Things in science can be so unpredictable. At its core, the scientific method can be boiled down to observation, hypothesis, and experiment. But sometimes you’ll make a set of observations, come up with a hypothesis, test it, and find that your original observations did not come anywhere near representing the full extent of what was going on. Those factors you didn’t account for cause your model to go awry, and you can end up having to reassess weeks, sometimes months (even years), worth of work.

There is also still so much we don’t know about basic AAV biology. We still have very little idea how certain things interact during viral packaging, or even during delivery and transduction. That makes it very difficult to predict what will happen. The only way to find out is by trying. Scientists are very curious people, but there are only a limited number of experiments you can perform. And as previously mentioned, if you make any assumptions that later turn out to be completely incorrect, the data you produce could end up being next to worthless. As a result you have to design your experiments very carefully, and be very picky about which questions to investigate first.

When not in the lab, how do you like to spend your time?

If I’m not here, and I’m not sleeping, I’m at the rock-climbing gym. I’m a very avid rock climber. I like to go outdoors a lot in the summer. I also really enjoy mountaineering. Some weekends in the winter I’ll be up hiking in the White Mountains. In the summer, I’m often traveling all over New England for rock climbing.

I’m also involved in several different volunteer efforts. I co-founded an alumni network for my undergraduate program, volunteer for STEM outreach to high school students in underrepresented demographics, and occasionally help out at a soup kitchen in Cambridge. I enjoy being exposed to so many different types of experiences, and value the perspectives they bring.

If you had to choose an entirely different career path what would it be?

Either a back-country guide or a farmer. It has to be something hands-on.

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 a privilege. It’s something that I don’t think a lot of people are really conscious of because you can get so wrapped up in your research and the process of trying to solve the next problem and getting to the next step. It’s easy to lose sight of the real-world impact that a project like this could have. The fact that I’ve found myself in a situation where I’m here at the Wyss Institute and working on such technologies makes me feel incredibly lucky. It’s a privilege to work with the people here who are insanely intelligent, very good at what they do, and so dedicated.

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