USC Viterbi’s Chung Lab has engineered a naturally derived particle for powerful therapies against cardiovascular and kidney diseases.

Have you seen the latest EV models?

Nope, not the Tesla Model 3. Think way smaller. And with better safety features.

The lab of Eun Ji Chung, founding director of the Transformative Center for Nanomedicine and Drug Delivery, is unveiling a new fleet of extracellular vesicles (EVs). These EVs, however, can fight heart disease.

Chung is an expert in drug delivery, gene therapy and nanomedicine. Her lab’s new work focuses on EVs — tiny, natural structures released by our own cells to communicate with other cells.

“Our cells naturally produce these natural nanoparticles,” Chung explained. “So, we genetically engineered the cell to produce those EVs in a more therapeutic manner than what they would normally be secreting.”

In short: Imagine a natural, built-in delivery system within your body, one that can be programmed to fight heart and kidney disease. This is the cutting-edge reality being shaped by biomedical engineers at USC Viterbi School of Engineering. Unlike synthetic particles, EVs can be genetically engineered to enhance their healing power, offering a safe and precise approach to medicine.

Cardiovascular disease and kidney disease are immense global health challenges. According to the U.S. Centers for Disease Control and Prevention, chronic kidney disease impacts over 1 in 7 adults, while heart disease remains the leading cause of death.

Atherosclerosis, in which plaque builds up in arteries, affects nearly half of all Americans between 45 and 84, often without symptoms, according to the National Institutes of Health. Current treatments mostly rely on cholesterol-lowering statins. Chung’s team recognized EVs’ natural role as the body’s intercellular delivery system, engineering the particles to boost a naturally occurring microRNA that specifically targets vascular smooth muscle cells, which are responsible for plaque formation.

“The therapeutic cargo is typically at low levels in EVs, so we engineer the cell to really boost it up,” Chung said. “Now, what they’re secreting performs thousands of times better in terms of therapeutic effect.”

In head-to-head comparisons, the engineered EVs proved significantly more effective than synthetic nanoparticles at reducing plaque formation.

“We did a dose match, and the EVs have a much better potency. So, not only are they natural, but something about their properties allows them to go inside the cell to a greater extent,” Chung said.

The Chung Laboratory is also exploring how EVs can treat autosomal dominant polycystic kidney disease (ADPKD), an inherited form of aggressive kidney disease leading to cyst growth and kidney failure.

Chung and her team are investigating using urinary EVs from healthy kidney cells, which contain functional proteins and RNA missing in ADPKD patients. In mouse studies, this approach successfully slowed cyst development and reduced disease without adverse effects.

“In genetic kidney diseases like ADPKD, patients have a certain mutated version of a gene, and that gives either no protein or a dysfunctional protein,” Chung said. “But if you get the EVs from a healthy donor, those EVs are loaded with the normal version of the protein.”

This work highlights EVs’ immense potential as an adaptable, naturally derived therapeutic tool.

“I feel EVs really are the next wave of nanotherapeutics,” Chung said.