Genetic medicines, in which molecules of DNA or RNA are the therapeutic agents, hold enormous promise for treating diseases ranging from genetic or inflammatory disorders to cancer. Although several of these therapies are currently being investigated or used to treat dozens of maladies, getting them precisely to where they’re needed in the body has been challenging.

Over the last decade, Daniel Siegwart, Ph.D., Professor in the Departments of Biomedical Engineering and Biochemistry and in the Harold C. Simmons Comprehensive Cancer Center, has made numerous strides toward delivery of nanoparticles carrying genetic medicines – work that has led to more than 300 patents and pending patent applications worldwide and two ongoing clinical trials.

Dr. Siegwart will detail these efforts as the first speaker of this year’s President’s Lecture Series on Feb. 13. The 4 p.m. lecture, “Innovation in Nanotechnology: From Vaccines to Novel Genetic Disease Treatment,” will take place in the Tom and Lula Gooch Auditorium.

In 2020, researchers elsewhere developed a new type of vaccine that relies on messenger RNA (mRNA) – a single-stranded genetic molecule that cells use to produce a specific protein – to prompt an immune reaction against the virus that causes COVID-19. Billions of doses of these vaccines have been administered worldwide, with few side effects.

But before the pandemic, Dr. Siegwart and other researchers were working diligently to develop genetic medicines for other conditions. Lipid nanoparticles, used in COVID-19 vaccines, have been a popular carrier for genetic medicines due to their biocompatibility, Dr. Siegwart explained. However, when these nanoparticles are delivered intravenously, they nearly universally end up in the liver due to their chemical similarity to the proteins that carry cholesterol to and from this organ.

“This is great news for diseases that affect the liver,” Siegwart said. “But if we want to treat diseases in other organs, we need to be creative about how we get our gene editing machinery there.”

In 2020, Dr. Siegwart and his colleagues first reported a system they developed and named Selective Organ Targeting, or SORT. By adding an extra component to the usual recipe for lipid nanoparticles, the researchers could adjust the charge of these drug carriers at will. These small but significant changes directed delivery of nanoparticles to specific locations – including the lungs, spleen, bone marrow, muscle, lymph nodes, and cancerous tumors – where they released their genetic cargo inside cells. There, the mRNA in these genetic medicines caused cells to produce proteins that effectively replaced those that were damaged or missing.

These findings, named in Nature as one of “Seven Technologies to Watch in 2022” and cited more than 1,300 times, formed the basis for UTSW spin-off ReCode Therapeutics. Therapies developed through this company are currently in clinical trials for cystic fibrosis and primary ciliary dyskinesia, diseases that primarily affect the lungs.

(Dr. Siegwart is a co-founder of ReCode Therapeutics and receives personal compensation from the company. UT Southwestern holds equity in ReCode.)

Other groundbreaking research from Dr. Siegwart’s team has included developing nanoparticles that go deep into tumors to transport drugs and activate an immune response, effectively stopping the growth and spread of liver and ovarian tumors in mice. Another study led by Dr. Siegwart, published in PNAS, demonstrated how genetic material tagged with a “cellular ZIP code” could prompt cells to secrete protein drugs into the bloodstreams of mice, thus successfully treating psoriasis and various forms of cancer. Using the body as the biofactory and pharmacy could someday allow patients to receive such treatments at home instead of in a hospital. His lab also works with mRNA and has provided advice to companies that make the vaccines for COVID-19.

Dr. Siegwart’s breakthrough work has been recognized recently with his election to the National Academy of Inventors. His patents and pending patent applications worldwide cover several fields including chemical compound compositions, drug and gene delivery systems, methods of targeting nanoparticles to organs and cells, and engineered nucleic acid sequences. He has co-founded multiple biotechnology companies. In addition, he recently was selected as a National Academy of Medicine (NAM) Emerging Leader in Health and Medicine Scholar – one of only 10 scientists and physicians from across the United States appointed to three-year terms who will be addressing topics shaping the future of health and medicine for the NAM.

Dr. Siegwart became interested in nanoparticle directed delivery after earning his undergraduate degree in biochemistry at Lehigh University, his doctoral degree in chemistry from Carnegie Mellon University, and postdoctoral training at the Massachusetts Institute of Technology in chemical engineering. While growing up in a blue-collar neighborhood in Pittsburgh, his parents encouraged him to explore his curiosity and stressed the importance of taking steps to achieve a goal.

“Simply put, I love ideas,” Dr. Siegwart said. “It’s just really fun and exciting to dream up new ideas, work on them with my colleagues, and use our creativity to pursue solutions that can address medical problems.”