For the next 40 years, Minnesota’s older demographic will make up the largest part of the state’s population. During this period, neurological disorders like Alzheimer’s disease and brain cancer, more prevalent in older adults, will pose a growing concern for the state. The number of people with Alzheimer’s and other dementias is expected to grow dramatically in the near future, affecting more than 200,000 Minnesotans by 2050 at an annual cost of $20 billion, according to a report prepared for the Alzheimer’s Association. Meanwhile, there are about 75,000 new cases of brain cancer each year in the U.S., which is also more common in older adults.
A team of University of Minnesota researchers spanning many academic disciplines has set out to improve treatments for these two diseases through the use of DNA nanotechnology — microscopic structures that are built from DNA. The structures — so tiny that 3,300 of them side by side would match the width of a human hair — have been used as containers for carrying drug treatments to specific parts of the body. When it comes to treating the brain, however, they fall short, getting stopped by white blood cells that guard the blood-brain barrier — a wall between the circulatory system and brain cells.
Lead researcher Efie Kokkoli, Ph.D., is developing a type of tube-shaped DNA structure that more effectively carries drug therapies past the blood-brain barrier, allowing drug treatments developed by her fellow researchers to more effectively reach the brain and treat those with neurological diseases. The project is part of the state-funded MnDRIVE Transdisciplinary Research Program, where researchers from different departments work beyond the limits of their disciplines to address complex challenges.
“To make treatments for these diseases more effective, we needed to find a smarter way of getting them to the brain,” said Kokkoli, a professor in the Department of Chemical Engineering and Materials Science with the College of Science and Engineering. Rod-shaped nanoparticles are more successful at delivering treatments to the brain compared to spherical nanoparticles, according to a University of California study. Therefore, Kokkoli explains, “by placing a drug therapy inside a DNA nanotube, we can safely and effectively send drug treatments through the body, ensuring the right therapies are able to have the greatest effect against brain diseases.”
Assembling DNA nanostructures can be slow, complicated and expensive, often requiring one long strand of DNA and hundreds of shorter pieces that act as staples to hold the structure together. Through her research, Kokkoli found an alternative way of engineering the DNA nanotubes into a type of “nanotape” that twists itself to form a solid tube much like a metal spring does when compressed. Unlike other DNA nanotubes that slowly come together from hundreds of different DNA sequences by adjusting their environment, Kokkoli’s discovery, using DNA-amphiphiles (molecules that have sections that love the water and sections that hate the water), can self-assemble in a matter of minutes in water from multiple copies of only one DNA-amphiphile molecule. The breakthrough provides a faster, easier and more robust way to produce drug delivery containers.
Putting the tubes to work
With an improved method for delivering brain therapeutics in hand, the researchers’ next step in the MnDRIVE project is to test new treatments to deliver through it. Scott McIvor, Ph.D., professor in the Department of Genetics, Cell Biology and Development in the U’s College of Biological Sciences, is designing the genetic material that will be delivered with the DNA nanotubes to kill cancer cells. McIvor will begin his research with gene sequences that have been known to work, but eventually will move on to designing new sequences that not only target cancer cells, but produce a specific molecule that sensors can pick up to indicate the treatment is working. Working alongside him will be Walter Low, Ph.D., a professor in the Department of Neurosurgery and expert in glioblastoma multiforme — the most common and aggressive form of brain cancer — whose expertise on the disease can help direct treatment.
Meanwhile, Karen Ashe, M.D., Ph.D., a professor with the U’s Department of Neurology and an expert in Alzheimer’s disease, will help develop a model for testing Alzheimer’s drugs using DNA nanotubes. Her preclinical trials in mice will allow the researchers to gauge how effective new treatments are for patients living with Alzheimer’s.
A new approach to allergy detection
While DNA nanostructures have huge potential in disease treatment, their use doesn’t end there. Ted Labuza, Ph.D., professor in the Department of Food Science and Nutrition with the College of Food, Agricultural and Nature Resource Sciences, will study how to use the DNA-amphiphiles to detect food allergens, both in processed food and on surfaces where food is prepared. Food allergies can cause life-threatening reactions and are a growing public health concern, affecting 4 to 6 percent of children in the U.S., according to the Centers for Disease Control and Prevention.
Current tests for food allergens are limited by the need for experienced operators, fluorescent dies and a lot of time. By using Kokkoli’s DNA-amphiphiles, Labuza aims to create sensors that work on their own to detect food proteins in a matter of seconds, with no trained operator necessary. Using this technology, for example, someone could swab a countertop to check for traces of milk proteins, determining whether that countertop will contaminate foods that otherwise do not contain milk. The practice could help prevent cross-contamination, where allergens work their way into foods meant to be safe for those with allergies to eat.
Navigating new waters
While other researchers dig into the science behind using DNA nanotechnology, professor Susan Wolf, J.D., a law and bioethics expert who chairs the U’s Consortium on Law and Values, is analyzing the policy issues raised by the technology, its use in humans during clinical trials and its future wide-scale use. Using DNA nanotechnology combines two traditionally separate fields, each with its own regulations. Wolf is leading an interdisciplinary group of top scholars from across the country to perform this analysis and issue recommendations for how to integrate oversight of genetic engineering with oversight of nanobiotechnology.
“DNA nanotechnology is a perfect example of emerging technology raising questions about how to support responsible innovation, eventual human trials and public understanding,” Wolf said. “As we develop new applications for DNA nanotechnology, we are also proactively considering how best to regulate and guide this promising technology. By examining the law, ethics and policy involved, we can develop recommendations for how to oversee the emerging field and encourage scientific advances while still controlling risk.”
This project is supported by MnDRIVE, a landmark partnership between the university and the state of Minnesota that aligns areas of university strength with the state’s key and emerging industries to advance new discoveries that address grand challenges.