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Nanobot Designed to Kill Hepatitis C virus

By BiotechDaily International staff writers
Posted on 31 Jul 2012
Scientists have moved closer to treating diseases on a cellular level by creating a particle that can be programmed to shut down the genetic production line that generates disease-related proteins. In laboratory tests, these newly created “nanorobots” all but eradicated Hepatitis C virus infection. The programmable characteristics of the particle make it potentially useful against diseases such as cancer and other viral infections.

The research effort, led by Dr. Y. Charles Cao, a University of Florida (UF; Gainesville, USA) associate professor of chemistry, and Dr. Chen Liu, a professor of pathology and endowed chair in gastrointestinal and liver research in the UF College of Medicine, was published online July 23, 2012, in the journal Proceedings of the National Academy of Sciences of the USA (PNAS). “This is a novel technology that may have broad application because it can target essentially any gene we want,” Dr. Liu said. “This opens the door to new fields so we can test many other things. We’re excited about it.”

During the past 50 years, nanoparticles have emerged as a practical foundation for new ways to diagnose, monitor and treat disease. Nanotechnology is already in use in medical settings, such as in genetic testing and for pinpointing genetic markers of disease. Moreover, several related therapies are at varying stages of clinical trial.

The Holy Grail of nanotherapy is an agent so intensely selective that it enters only diseased cells, targets only the specified disease process within those cells, and leaves healthy cells unharmed. To show how this can work, Dr. Cao and colleagues created and evaluated a particle that targets Hepatitis C virus (HCV) in the liver and prevents the virus from making copies of itself.

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 50 percent of patients, according to studies published in the New England Journal of Medicine (NEJM) and other journals. Side effects vary widely from one medication to another, and can include flu-like symptoms, anemia, and anxiety.

Dr. Cao and colleagues sought to improve on the idea of interfering with the viral genetic material in a way that enhanced therapy effectiveness and reduced side effects. The particle they created can be customized to correlate with the genetic material of the desired target of attack, and to sneak into cells unseen by the body’s intrinsic defense mechanisms.

Recognition of genetic material from potentially harmful sources is the basis of valuable treatments for a number of diseases, including cancer, which are associated with the production of harmful proteins. It also has potential for use in detecting and killing viruses used as bioarsenals.

The new virus-destroyer, called a nanozyme, has a backbone of tiny gold particles and a surface with two main biologic components. The first biologic portion is an enzyme that can destroy the genetic recipe-carrier, called messenger RNA (mRNA), for producing the specific disease-related protein. The other component is 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 combination solves the problem. “They completely change their properties,” Dr. Cao said.

In laboratory tests, the treatment led to nearly a 100% decrease in HCV levels. Moreover, it did not trigger the body’s defense processes, and that reduced the chance of side effects. Still, further testing is needed to determine the safety of the approach.
Future therapies could theoretically be in pill form. “We can effectively stop hepatitis C infection if this technology can be further developed for clinical use,” said Dr. Liu, who is a member of the UF Shands Cancer Center.

The UF nanoparticle design takes inspiration from the Nobel prize-winning discovery of a process in the body in which one part of a two-component complex destroys the genetic instructions for manufacturing protein, and the other part serves to restrain the body’s immune system attacks. This complex controls many naturally occurring mechanisms in the body, so agents that imitate it have the potential to take over the production of proteins required for normal function. The UF-developed therapy fools the body into accepting it as part of the normal processes, but does not interfere with those processes.

“They’ve developed a nanoparticle that mimics a complex biological machine--that’s quite a powerful thing,” said nanoparticle expert Dr. C. Shad Thaxton, an assistant professor of urology at the Feinberg School of Medicine at Northwestern University (Chicago, IL, USA). “The promise of nanotechnology is extraordinary. It will have a real and significant impact on how we practice medicine.”

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