Montana State University to figure out tricky viruses, adapt for gene therapy

Viruses have an uncanny ability to trick cells into letting them inside. Once inside, they take over, says Brian Bothner, a faculty member in Montana State University's Center for Bio-Inspired Nanomaterials and the Department of Chemistry and Biochemistry.

Now -- with the assistance of an MSU senior who helped renovate the campus duck pond -- Bothner has a $1.2 million grant to tap into that talent.

The National Institutes of Health recently awarded Bothner a four-year grant to understand how viruses assemble themselves, enter cells and seize control. He and his collaborators will use that knowledge to build viruses that can carry genes to specific targets. A doctor might want to send a healthy gene to a heart muscle, for example, or an optic nerve.

"We study viruses from lots of different angles," Bothner said. "This is from a biophysical standpoint."

Working with researchers Mavis Agbandje-McKenna and Robert McKenna from the University of Florida, Bothner will study four types of the Adeno-associated Virus (AAV) to learn more about their structures and tricks for getting inside cells. Nick Muzyczka, a molecular biologist, also at the UF, will use those findings to build specialized AAVs.

"This could dramatically expand their uses as a delivery vehicle," Bothner said.

AAVs are unique human viruses that are popular in gene therapy, partly because they don't cause any diseases in humans or animals.

"If you mess up, you won't get someone sick with this virus," Bothner commented.

His Florida collaborators have used AAV in previous projects, and the UF has a large medical school that uses AAV in gene therapy, Bothner said. Despite that experience, however, researchers still don't know exactly how AAV find and enter the right cells. Unraveling the mystery and learning how to build made-to-order AAVs is Bothner's goal.

MSU graduate and undergraduate students will be involved in that effort. One undergraduate student, in particular, had a significant part in obtaining the NIH grant in the first place, Bothner said.

Shannon Kruse is a biochemistry major whose family, Kruse Enterprises, renovated the MSU duck pond in 2008 and was the contractor for the new Alumni Plaza in front of MSU's Chemistry and Biochemistry Building. Kruse also works in Bothner's laboratory with funding from INBRE, a statewide program to enhance biomedical research. It was there that she conducted a variety of experiments that helped convince the NIH to award the grant, Bothner said.

"She played a major role in getting the data that allowed us to get the grant," Bothner said.

Kruse tested several AAVs to see how they reacted to fluctuating temperatures and pH levels. That was important, Kruse said, because viruses experience pH changes when they enter a cell. Bothner added that Kruse's experiments also narrowed down the number of AAVs to the ones that will be used in the research project.

Kruse said she enjoys working with her family. She talked about the fun she had while restoring the duck pond in 2008. In the long run, however, she will probably attend graduate school and eventually pursue a career in pharmaceutical research. She originally majored in chemical engineering, but switched majors after taking a required course in organic chemistry.

"I loved the chemistry so much I wanted to be able to take more, so I looked into chemistry majors and felt that biochemistry was the best fit, and it has been," Kruse said. "I love it."

Source: Montana State University