(left) Y. Charles Cao, Ph.D. (right) Chen Liu, M.D., Ph.D./Photo by Jesse S. Jones

UF researchers have moved a step closer to treating diseases on a cellular level by creating a tiny particle that can be programmed to shut down the genetic production line that cranks out disease-related proteins.

In laboratory tests, these newly created “nanorobots” all but eradicated hepatitis C virus infection. The programmable nature of the particle makes it potentially useful against diseases such as cancer and other viral infections.

The research effort, led by Y. Charles Cao, Ph.D., a UF associate professor of chemistry, and Chen Liu, M.D., Ph.D., a professor of pathology and endowed chair in gastrointestinal and liver research in the UF College of Medicine, was described in the Proceedings of the National Academy of Sciences in July.

“This is a novel technology that may have broad application because it can target essentially any gene we want,” Liu said. “This opens the door to new fields so we can test many other things. We’re excited about it.”

During the past five decades, nanoparticles have emerged as a viable foundation for new ways to diagnose, monitor and treat disease. Nanoparticle-based technologies are already in use in medical settings, such as in genetic testing and for pinpointing genetic markers of disease. And several related therapies are at varying stages of clinical trial.

The Holy Grail of nanotherapy is an agent so exquisitely selective that it enters only diseased cells, targets only the specified disease process within those cells and leaves healthy cells unharmed.

With funding from the National Institutes of Health and other sources, Cao and colleagues created and tested a particle that targets hepatitis C virus in the liver and prevents the virus from making copies of itself.

Hepatitis C infection causes liver inflammation, which can eventually lead to scarring and cirrhosis. Current hepatitis C treatments involve the use of drugs that attack the replication machinery of the virus. But the therapies are only partially effective, on average helping less than half of patients.

Cao and colleagues wanted to improve on the concept of interfering with the viral genetic material in a way that boosted therapy effectiveness and reduced side effects. The particle they created can be tailored to match the genetic material of the desired target of attack, and to sneak into cells unnoticed by the body’s innate defense mechanisms.

Recognition of genetic material from potentially harmful sources is the basis of important treatments for a number of diseases, including cancer, that are linked to the production of detrimental proteins. It also has the potential for use in detecting and destroying viruses used as bioweapons.

The new virus-destroyer, called a nanozyme, has a backbone of tiny gold particles and a surface with two main biological components. The first biological portion is a type of protein called an enzyme that can destroy the genetic recipe-carrier, called mRNA, for making the disease-related protein in question. The other component is a large molecule called a DNA oligonucleotide that recognizes the genetic material of the target to be destroyed and instructs its neighbor, the enzyme, to carry out the deed. By itself, the enzyme does not selectively attack hepatitis C, but the combo does the trick.

In laboratory tests, the treatment led to almost a 100 percent decrease in hepatitis C virus levels. Additional testing is needed to determine the safety of the approach. Future therapies could potentially be in pill form.

“We can effectively stop hepatitis C infection if this technology can be further developed for clinical use,” Liu said.