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Ralph Tripp is working to detect, prevent and stop what makes us sick.


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 developing new ways to fight disease and illness.
 
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, Tripp has now developed several drugs to treat respiratory viruses such as respiratory syncytial virus (RSV), which poses a significant threat to the very young and elderly.
 
This autumn, one of Tripp’s drugs targeting RSV will enter the final phase of human testing required to be authorized by the Food and Drug Administration. If approved, it would be the first of its kind to target a specific virus – and would help save thousands of lives each year in the U.S. alone.
 
But that new drug treatment is only the beginning of what Tripp’s research could lead to.
 
For the first time, Tripp and his research team have shown that the RNAi gene silencing process they’re exploring 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, Tripp and UGA doctoral student Wenliang Zhang showed that administering a “small interference RNA” (siRNA) drug in mice prevented RSV infection – it actually provoked 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,” Tripp says. “We were able to reduce the replication of the virus enough to prevent the development of disease, yet still induce potent immunity later on.”
 
Preliminary data from Tripp’s research shows that a similar approach would likely have the same effect on other diseases. So he’s embarked on new efforts to develop synthetic anti-viral drugs that act like vaccines for influenza and a variety of other significant human viruses.
 
Research into RNA interference can be transformative. It’s a process that holds great promise for controlling genes and their activity, including gene expression that can prevent or promote cell growth as well as mount a defense against a viral threat. Tripp’s research explores how these small RNA molecules can work to silence gene expression, so that a virus is unable to “co-opt” the host genes it needs to replicate.
 
A fundamental question is, which genes should be targeted for silencing expression? In 2010, Tripp and fellow researchers identified more than 300 potential gene targets for influenza. The targets have only expanded since: Today, Tripp is applying his RNAi science to develop first-in-class cell lines that can yield more vaccine – without changing the manufacturing process – to help eradicate an array of diseases, including polio, measles and rotavirus.
 
A cost-effective method for increasing vaccine production would have a huge effect on the health of at-risk populations. High-performance vaccine cell lines would speed up multiple steps in the current process to produce vaccines, thus reducing costs. The savings would enable manufacturers, distributors and the medical community at large to focus their efforts and resources on the growing landscape of challenges facing the developing world.
 
Tripp’s latest research is conducted in collaboration with the Bill and Melinda Gates Foundation, CDC and ThermoFisher Scientific. While its potential is phenomenal, his contributions to human health don’t end there.
 
Three years ago, 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, 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,” Tripp says, adding that such detection now requires lab testing procedures that can take weeks to process.
 
The SERS technology is now being used to detect Hendravirus in horses in Queensland, Australia. The U.S. Navy is also using it to detect bacterial infections in wounded warriors. Closer to home, Emory University is using Tripp’s invention to detect RSV and influenza in nasal secretions of hospitalized infants at Emory University in Atlanta.
 
With the help of GRA Ventures, the commercialization program of GRA, Tripp launched a company, Argent Diagnostics, to bring the technology to market. His partners in the venture include Richard Dluhy and Yiping Zhao at UGA and Lawrence Bottomley at Georgia Tech. Tripp also has formed two other companies, HyperCell, LLC and VacCell, to advance antibody therapeutics in animal health and agriculture, as well as develop new vaccine cell lines for veterinary and related applications.
 
Before coming to UGA in 2004, Tripp was the immunology 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, 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 Tripp as an Eminent Scholar and funded 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 10 years at UGA, Tripp has brought in more than $ 40 million in private investment and government grants. He and GRA Scholar Steve Dalton have co-formed the new Center of Molecular Medicine at UGA, and Tripp has won drug development contracts with several pharmaceutical companies and has recruited several prominent scientists to UGA.

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Left: GRA Eminent Scholar Ralph Tripp has discovered a new drug (now completing FDA testing), invented a viral detection device — and made major advances toward increasing vaccine yields to combat polio, measles and other diseases. Above: Respiratory syncytial virus, or RSV, a front-line target of Tripp's work.
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