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Grant funds Virginia Tech research for genetic therapy

The National Institutes of Health (NIH) has awarded a $2.3 million grant to a Virginia Tech research team led by Theresa Reineke, an associate professor of chemistry in the College of Science, to continue its biomedical research into new medicines that have the potential for better results and fewer side effects.

   

Theresa Reineke (right) works with two members of her research team, Karina Kizjakina (left) and Antons Sizovs. Theresa Reineke (right) works with two members of her research team, doctoral students Karina Kizjakina (left) and Antons Sizovs.

The grant gives one example of the attention Reineke and her team has generated in the world of genetic drug research. The group is creating carbohydrate-based polymers for the delivery of genetic drugs to combat both cancer and heart disease. The newly developed molecules can travel into cells, deliver genetic drugs, and carry a tracking ability so that scientists can follow their movements in living systems. 

Reineke’s New Innovator grant from the NIH funds research that is in its earliest stages and holds potential for exceptionally high impact. These awards are designed to stimulate highly innovative research and support promising new investigators. According the NIH, many new scientists have exceptionally innovative research ideas, but lack the preliminary data required to fare well in the traditional NIH peer review system.

“This grant will allow us to gain a better understanding of the cellular mechanisms involved in the delivery of polymeric drug carriers for both illnesses,” Reineke said. “Traditional drugs are aimed at treating disease at the protein level. Genetic drugs — such as those that can alter or control gene expression — aim to treat disease at the genetic level and have the added benefit of being more specific for their medicinal target.”  An example would be a genetic message that would arrest tumor growth.

“Synthetic polymers that are compatible with biological systems are playing important roles in the diagnosis and treatment of many diseases,” Reineke said. “Understanding how biomaterials interact with and affect living systems is one of the most important and fundamental problems in biomedical research.”

Delivering a powerful punch

A challenge has been that DNA and RNA drugs – pieces of genetic code that store information and instructions – cannot diffuse through the cell the way traditional small molecule drugs can.

   

Theresa Reineke's research team Theresa Reineke's (far left) research team includes doctoral students (from left, front) Giovanna Grandinetti, Dan Buckwalter, Lian Xue, (from left, back) Hao Lu, Antons Sizovs, Karina Kizjakina and Vijay Taori.

"We needed a vehicle to carry them into cells," said Reineke. One such vehicle has been engineered viruses. Reineke's group has been working on a different solution.

The scientists created novel polycations, which are polymer chains with positive charges. DNA is a polyanion, a polymer with negative charges. The Reineke group's supramolecule has options. It contains chemistry that binds and compacts nucleic acids – pieces of the DNA – into nanoparticles. It also incorporates a group of rare-earth elements known as lanthanides. The repackaged DNA is protected from damage as it travels into the cells, and the lanthanides allow visualization of the delivery into cells.

   

In this image the polymer signal is red and the DNA signal is green. This image shows successful delivery of DNA into a human cervical cancer cell using Theresa Reineke’s DNA delivery agent. In this image the polymer signal is red and the DNA signal is green. Having information about spatial location of delivery agents in the cell provides researchers with the ability to design more effective DNA carriers.

"In our experiments, these delivery beacons provide the ability to track DNA delivery into living cells," said Reineke. "They provide the potential for tracking genetic therapies within the living body," she said.

At the nanometer or cellular scale, the researchers are able to track the polymers using sensitive microscopes, which capture the nanoparticle luminescence. At the sub-millimeter or tissue scale, magnetic resonance imaging (MRI) is used to see where the nanoparticles are going.

"This ability to track the movement and delivery of a gene-based drug provides an opportunity to understand the mechanism of delivery and monitor efficacy in real time, so that we can develop better materials for delivering genetic therapeutics and ultimately better treatments," Reineke said.

The research was published in the Proceedings of the National Academy of Sciences in fall 2009. Download the abstract

The research has also been supported by Reineke's Alfred P. Sloan Research Fellowship and by the Camille Dreyfus Teacher-Scholar Awards Program.

  • For more information on this topic, contact Catherine Doss at (540) 231-5035.

Recognition for Theresa Reineke

    Theresa Reineke

Awards and recognition for Theresa Reineke's work include:

  • 2009 NIH Director's New Innovator Award
  • 2008 Camille Dreyfus Teacher-Scholar Award
  • 2007-09 Kavli Fellow (National Academy Frontiers of Science Program)
  • 2007 Alfred P. Sloan Foundation Fellow
  • 2007 "30 in their 30s" in Ohio Bioscience Award
  • 2006 Lowenstein Scholar (University of Cincinnati)
  • 2005 Beckman Young Investigator Award
  • 2005 Sigma Xi Outstanding Young Investigator Award
  • 2005 National Science Foundation Early Career Development Award
  • 2003 American Chemical Society (Division of Polymeric Materials: Science and Engineering), Arthur K. Doolittle Award
  • 2002 National Institutes of Health, National Research Service Award

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