By silencing gene expression, GRA Eminent Scholar Ralph Tripp is breaking new ground in drug and vaccine development
What if a virus that invades a cell could be kept from replicating itself?
That simple question is at the heart of research being conducted by Ralph Tripp, a renowned viral immunologist and GRA Eminent Scholar at the University of Georgia. And the answer has profound implications on the development of new ways to fight disease and illness.
Dr. Tripp and his research team have broken new ground in understanding how cells in the body can silence genes to inhibit the signaling required to replicate a virus – a process known as RNA interference (RNAi). Based on that new knowledge, Dr. Tripp developed a drug to treat respiratory syncytial virus or RSV, a respiratory virus that poses a threat to the elderly and very young.
This fall, the RNAi drug enters the final phase of human testing. If approved, it would be the first of its kind and would save thousands of lives each year in the U.S. alone.
But that new drug treatment is only the beginning of what Dr. Tripp’s research could lead to.
For the first time, Dr. Tripp and his research team have shown that the RNAi gene silencing process could also be a tool to develop a new class of vaccines.
In a study published in the December 2009 issue of the Journal of Virology, Dr. Tripp and UGA doctoral student Wenliang Zhang showed that administering a “small interference RNA” (siRNA) drug in mice prevented RSV infection and allowed for a vaccine-like immune response to infection.
“This is the first study of its kind to show that siRNA can be used to improve the immune system’s memory response to an infectious agent,” Dr. Tripp says. “We were able to reduce virus replication enough to prevent the development of disease but still induce potent immunity later on.”
Preliminary data from Dr. Tripp’s research shows that a similar approach would likely have the same effect on other diseases. So he has embarked on new research to help develop synthetic anti-viral drugs that act like vaccines for influenza and a variety of significant human viruses..
Research into RNA interference is regarded as a transformative, if fairly recent, event in science, one that holds great promise for treating or fighting off infection. Fundamentally, RNAi is a process that allows cells to control genes and their activity, including gene expression that can prevent or promote cell growth or mount a defense against a viral threat. Dr. Tripp’s research explores how small RNA molecules can work to silence gene expression so that a virus is unable to send the signals needed to create genetic copies of itself.
A fundamental question is, which genes should be targeted for silencing expression? In 2010, Dr. Tripp and fellow researchers identified >300 potential gene targets for influenza.
“This first screening is pretty broad, so we validated the screening and narrowed the list to 30,” Dr. Tripp explains. “We then picked and validated 12 genes that are the best candidates in real-life scenarios.”
Dr. Tripp’s earlier success in fighting RSV – first with the new drug treatment, later with the immunity induced in mice – addresses a sly health threat. RSV is the most prevalent cause of hospitalization in infants and young children and is often mistaken for the flu. Some 90,000 people in the United States are hospitalized with RSV each year. About 5,000 of them die.
More striking, research by the Centers for Disease Control and Prevention (CDC) has revealed that perhaps half of all pneumonia and influenza deaths blamed on the flu are likely caused by RSV.
As notable as Dr. Tripp’s exploration of RNA interference is, his contributions to human health don’t end there – far from it.
Three years ago, Dr. Tripp and colleagues at UGA had another breakthrough in a technology that could detect viruses in a minute or less. The technology, called surface enhanced Raman spectroscopy (SERS), uses laser light to induce vibration of virus molecules on a silver nanorod surface. Raman spectroscopy then gives information on these vibrations in the form of a spectrum.
Because each spectrum is specific to the material being analyzed, a ‘molecular fingerprint’ of a detected virus is created. Using SERS, Dr. Tripp and team showed strains of viruses could be detected instantly.
The manifestation of this discovery is a handheld device that can be used to scan people and objects to determine the presence of viruses. “You could actually apply it to a person walking off a plane and know if they’re infected,” Dr. Tripp says, adding that such detection now requires laboratory testing procedures that can take days to weeks to process.
With the help of GRA’s VentureLab program, Dr. Tripp launched a company, Argent Diagnostics, to commercially develop the technology. His partners in the venture include Richard Dluhy and Yiping Zhao at UGA and Lawrence Bottomley at Georgia Tech.
Before coming to UGA in 2004, Dr. Tripp was the immunology section chief of the Respiratory and Enteric Viruses unit at the CDC. He conducts his work at UGA’s Animal Health Research Center in a 75,000-square-foot BSL3-Ag facility – one of two academic, non-federal labs capable of conducting research with high-containment pathogens on both small and large animals.
In his role at the CDC, Dr. Tripp was in regular contact with GRA Eminent Scholars from Emory University. He had not considered moving into academia, but when UGA approached him about becoming an Eminent Scholar, his familiarity with GRA’s program made him want to learn more. GRA not only named Dr. Tripp as an Eminent Scholar and funded Dr. Tripp’s position but also invested in a $2 million upgrade to the Animal Health Research Center, an investment that covered the purchase of sophisticated technology for research and commercial development.
In his six years at UGA, Dr. Tripp has brought in more than $ 10 million in private investment and government grants. He has won drug development contracts with several pharmaceutical companies and has recruited several prominent scientists to UGA, including Dr. Biao He from the Penn State University, Dr. Mark Tompkins from the FDA, and Dr. Robert Hogan from Southern Research Institute.
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