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Nanorobot can be programmed to target different diseases

By R&D Editors | July 16, 2012

University
of Florida 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, a UF 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, is
described online this week in the Proceedings of the National Academy
of Sciences.

“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—particles so small that tens of
thousands of them can fit on the head of a pin—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.

To
demonstrate how this can work, Cao and colleagues, with funding from
the National Institutes of Health, the Office of Naval Research and the
UF Research Opportunity Seed Fund, 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. The disease is transmitted via contact with
infected blood, most commonly through injection drug use, needlestick
injuries in medical settings, and birth to an infected mother. More than
3 million people in the United States are infected and about 17,000 new
cases are diagnosed each year, according to the Centers for Disease
Control and Prevention. Patients can go many years without symptoms,
which can include nausea, fatigue and abdominal discomfort.

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

Cao
and colleagues, including graduate student Soon Hye Yang and
postdoctoral associates Zhongliang Wang, Hongyan Liu and Tie Wang,
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
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.

“They completely change their properties,” Cao said.

In
laboratory tests, the treatment led to almost a 100% decrease in
hepatitis C virus levels. In addition, it did not trigger the body’s
defense mechanism, and that reduced the chance of side effects. Still,
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,” said 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 hold off the body’s immune system attacks.
This complex controls many naturally occurring processes in the body, so
drugs that imitate it have the potential to hijack the production of
proteins needed for normal function. The UF-developed therapy tricks 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 and co-founder of the
biotechnology company AuraSense LLC, who was not involved in the UF
study. “The promise of nanotechnology is extraordinary. It will have a
real and significant impact on how we practice medicine.”

Source: University of Florida

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