Most of us experience medicine as something simple: a tablet, a shot, relief. But for advanced therapies, especially genetic medicines, the hardest part often isn’t the “drug.” It’s the delivery.
On the Learning From Leaders podcast, UT Southwestern’s Daniel Siegwart, Ph.D., explains the delivery challenge his team put at the top of their list: “All nanoparticles go to the liver.” That default isn’t always a bad thing. In fact, liver delivery has enabled important advances. But it becomes a barrier when the disease is in the lungs, kidneys, brain, or elsewhere.
In this episode, Dr. Siegwart explains how his lab spent years identifying the mechanisms that determine where nanoparticles travel in the body and how altering those patterns could create new possibilities for patients.
Key Takeaways
- Nanoparticles are tiny spheres that can carry genetic medicines into cells.
- Many genetic medicines can’t enter cells on their own, which makes delivery essential.
- Dr. Siegwart’s team found ways to redirect nanoparticles from the liver to organs like the lungs.
- The same leadership habits that drive scientific breakthroughs, including clear goals, adaptability, and mentorship, also power biotech innovation in Dallas.
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“We spent the next five years elucidating those rules and now you have the blueprint, how to break the rules.”
Daniel Siegwart, Ph.D.
Delivery Breakthrough in Genomic Medicine
Dr. Siegwart explains nanoparticles as tiny spheres, smaller than the width of a human hair. His team works with lipid nanoparticles, which are made from the same kinds of molecules that help form the membranes around our cells. One colleague calls them “little balls of fat,” a phrase Dr. Siegwart likes because it is both accurate and easy to understand.
Nanoparticles matter because many genetic medicines cannot enter cells on their own. Lipid nanoparticles can carry and protect RNA- or DNA-based medicines, helping them reach the inside of cells where they can do their work.
Through the Siegwart Lab, his team develops nanoparticle technologies designed to deliver genetic medicines to specific tissues and organs.
“All Nanoparticles Go to the Liver.”
The liver is exceptionally good at filtering what circulates through the bloodstream. But that also means nanoparticles designed to carry genetic medicines often end up there, even when researchers want them somewhere else. So, his team went back to fundamentals. Why does the liver capture so many nanoparticles? What design features drive that outcome? And what changes could redirect delivery?
Dr. Siegwart describes a five-year effort to understand the principles behind organ targeting, shaped by chemistry, engineering, and physiology. Once they understood the rules, they could design ways to break them.
By adding specific components, the team helped nanoparticles avoid the liver and reach other organs, including the lungs, enabling genetic medicine delivery to lung cells in a new way. For patients, this is more than a scientific milestone. It may create new opportunities for treating genetic respiratory diseases, especially in cases where the limiting factor hasn’t been the concept of the medicine, but the challenge of getting it to the right cells.
Moving Discoveries Toward Patient Care
UT Southwestern is embedded in an environment of patient care, and Dr. Siegwart notes that even though he doesn’t see patients directly, he feels a responsibility to contribute science that can improve lives.
That’s also why commercialization and collaboration matter. Developing a drug requires significant time, expertise, and investment, and it often depends on assembling partners who can carry a discovery forward into clinical development.
Dr. Siegwart shares a mentor-inspired framework for what helps university discoveries move from the lab toward real-world impact:
- Protectable intellectual property
- Peer-reviewed validation
- A platform approach, not only a single product
- Experienced business leadership
It’s a reminder that breakthroughs don’t end at publication. Turning scientific ideas into medicines takes sustained effort, coordinated teams, and long-term support.
More Than Experiments: The Leadership Behind Breakthroughs
Dr. Siegwart describes something many people don’t expect about science. It’s deeply creative. Ideas can come from anywhere, and a big part of the work is turning an idea into something real in the lab.
He also notes that scientists are often trained to run experiments, not necessarily to lead teams, so leadership skills are often learned through mentorship and experience. Over time, he shaped a leadership approach that blends clarity with freedom.
- Provide enough detail and direction that people understand their mission and roadmap.
- Create enough space that they can explore, make mistakes, and learn, because sometimes those mistakes become discoveries.
He also shares an idea that applies far beyond the lab. Build teams of “volunteers, not hostages,” people who are motivated by real passion and purpose.
And as the Dallas–Fort Worth biotech community grows, he sees continued opportunity, especially as more local success stories create the next generation of leaders who can build and scale new companies here.
Advancing Research That Changes Lives
Dr. Siegwart connects scientific advancement to the broader mission shared across UT Southwestern’s ecosystem, and he acknowledges Southwestern Medical Foundation’s role in supporting and enriching research, education, and patient care in our region.
This work is a clear example of why long-term support matters. Spending years mapping the rules of biology, and then engineering ways to rewrite them, can expand what’s possible for patients in Dallas and beyond.
When researchers can redirect nanoparticles from the liver to the lungs, they aren’t just solving a technical problem. They are expanding the possibilities for therapies targeting conditions where improved delivery could lead to better outcomes, and helping ensure North Texas remains a place where discovery translates into real-world impact.
What’s Next: Smarter Delivery, AI, and the Future of Genetic Medicine
Looking ahead, Dr. Siegwart points to a future where genetic medicines can become more precise, more adaptable, and more widely applicable across disease areas. The next frontier is not simply discovering powerful RNA or DNA-based therapies. It is learning how to deliver them to the right cells, in the right tissues, at the right time.
That work will depend on smarter science. AI-enabled design methods are already becoming part of the broader genetic medicine landscape, helping researchers evaluate patterns, identify promising formulations, and learn more efficiently from what does and does not work. In this context, AI is not replacing scientific judgment. It is helping teams ask better questions, test more possibilities, and move through complex design challenges with greater speed and clarity.
Automation and high-throughput tools can also expand the number of ideas a lean research team can evaluate. For nanoparticle delivery, that means more “shots on goal” as scientists explore which chemical structures, lipid combinations, and targeting strategies may help medicines reach organs beyond the liver.
For patients, this matters because delivery can determine whether a promising therapy ever becomes practical. As researchers continue improving how genomic medicines move through the body, the field may unlock new approaches for conditions affecting the lungs, kidneys, brain, cancer, and other difficult-to-reach sites.
Why Genetic Medicine Innovation Matters to Southwestern Medical Foundation’s Work
Southwestern Medical Foundation exists to build sustainable support for innovative research, best-in-class medical education, and the highest standard of care. The Learning From Leaders podcast was created in that same spirit: to elevate knowledge exchange and strengthen collaboration among civic, business, philanthropic, and medical leaders across North Texas.
That is exactly what this conversation with Dr. Siegwart illustrates. Medical breakthroughs do not happen in isolation. They require patient-centered research, long-term investment, strong mentorship, commercialization pathways, and a community willing to support ideas before their full impact is visible.
When scientists at UT Southwestern develop new ways to redirect nanoparticles from the liver to organs like the lungs, they are doing more than solving a technical challenge. They are expanding what may one day be possible for patients who need better therapies, better delivery systems, and better answers.
This kind of progress reflects the Foundation’s long-term commitment to inspiring progress in medicine. By supporting the ecosystem where research, education, and patient care work together, Southwestern Medical Foundation helps ensure that bold ideas have the opportunity to move from the lab toward meaningful impact for North Texas and beyond.
FAQs
What are lipid nanoparticles (LNPs)?
Tiny lipid-based spheres that can carry genetic medicines into cells by protecting the payload and helping it cross cell membranes.
Why do nanoparticles often go to the liver?
Many nanoparticles end up in the liver by default due to how the body processes and filters circulating particles.
What’s new about lung-targeted delivery?
Dr. Siegwart’s team developed approaches that help nanoparticles avoid the liver and reach the lungs, enabling delivery where it previously wasn’t possible.
Why is delivery essential for genetic medicines?
Many RNA/DNA medicines can’t enter cells on their own, so they require a delivery system to reach the right location and work effectively.
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