Over time, viruses have evolved very efficient methods for making us sick, but a UT Dallas researcher thinks that same efficiency could be exploited to improve human health.
Dr. Jeremiah Gassensmith, assistant professor of chemistry and biochemistry in the School of Natural Sciences and Mathematics, recently received a Faculty Early Career Development (CAREER) Award from the National Science Foundation to investigate the use of viruses for precisely delivering therapeutic drugs to the body.
The five-year, $500,000 grant supports work that is a continuation of research originally done by two doctoral students in Gassensmith’s lab — Zhuo Chen and Candace Benjamin. Both will play lead roles in the new project.
Viruses are very simple organisms, consisting of genetic material wrapped up in a coating of proteins. When a virus invades a host, it injects that genetic material into the host’s cells, hijacking cell machinery to make many more copies of itself. The spread of the virus throughout the body makes the host sick.
“The environment and evolution have pressured viruses into being really stable natural nanoparticles, with all the properties needed to deliver cargo to specific cells,” Gassensmith said. “Conceptually, they’re an ideal drug-delivery system, and their persistence is a testament that nanotechnology can work in biological systems. Our idea is to take viruses that are noninfectious and teach them how to deliver drug therapy or gene therapy.”
The research team only uses viruses that infect plants or bacteria, so they have no effect on humans. And in most cases they’re not using the whole virus, just the viral capsid, which is the protein shell that surrounds and holds a virus’s genetic material.
“In our process, no viral genome is left inside the capsid, so they’re harmless,” Gassensmith said.
Capsids offer advantages over other proposed drug-delivery systems, he said. Because they are inherently biodegradable, they would not be expected to accumulate for an extended time in organs or tissues, as harder, inorganic nanoparticles, such as metals, might.
Gassensmith’s research team, which includes several graduate students and undergraduates, is focused on adapting the viral capsids to deliver cytotoxic drugs, which kill cells.
“Using viruses that don't infect people means they need to be taught how to find human cells and deliver drugs or genes. That’s where chemistry comes in,” he said.
One of the challenges is that there are only a handful of chemical reactions that might successfully bind the capsid proteins to other molecules, such as molecules that would help the capsid home in on a specific type of cell. The chemical reactions also have to work well in water. Gassensmith’s group has already developed new reaction methods that can attach substances to the surface of the viral capsid to target cancer or to work as MRI contrast agents.
“One of the added benefits of these new reactions is that since they work in water and at room temperature, they're pretty environmentally friendly,” Gassensmith said. “Plus, using these reactions has let us do some interesting things, like release drugs from the surface of the virus using light.
“We also think we can expand the function for gene therapy, to deliver RNA (ribonucleic acid) to targeted cells and basically turn on or turn off selected protein expression,” he said.
The team is working with isolated cells, and the next step is to evaluate the approach in animal models. It could be many years before this type of therapy is used in patients, Gassensmith said, “but the possibilities are very enticing.”
The NSF CAREER Award recognizes early career faculty who have demonstrated exceptional research abilities and supports their teaching and outreach activities.
In addition to leading the science investigation, Benjamin and Chen are overseeing an outreach project aimed at K-12 students and their parents. The Gassensmith lab is creating a free, web-based comic designed both to entertain and to educate by telling stories about how nanomaterials interact with the body and how they might be used in future drug-delivery systems.
The goal is to create multilingual comics and videos to promote scientific literacy and engage a global audience.
“I know French, other students in the lab know Vietnamese, Arabic, Spanish and Chinese, and we’re reaching out to others who can help us translate into other languages,” Benjamin said.
Gassensmith said the project offers opportunities to work with other departments on campus, such as the School of Arts, Technology, and Emerging Communication.
“UT Dallas has a bunch of students from different backgrounds with many skill sets who speak different languages, so we hope to build on those assets to globalize science education,” he said.