Researchers in the making:
Clamping down on hepatitis B
An AHFMR Student looks for ways to disable a stubborn form of the dangerous liver virus.
Hepatitis B is the world's most prevalent serious liver infection. About 2 billion people around the world have been infected, generally through the transmission of blood or other body fluids. With the help of current treatments, most of those 2 billion will manage to clear the virus and recover. But around 10% will not; they will develop chronic infections that can lead to even more serious long-term illnesses, such as liver cancer. For infants and children, the percentage is much higher: 90% of infants and 50% of young children infected with hepatitis B will develop chronic infections.
These chronic infections are caused by a special form of the hepatitis B virus that develops in the liver: a virus consisting of a very stable type of DNA (called cccDNA) that is extremely difficult to attack directly with drugs or treatments. But AHFMR Student Kimberley Zimmerman may have found a way to do just that.
Zimmerman studies zinc finger proteins-so called because each protein is composed of a number of finger-like structures, with zinc ions in the middle to hold them together. Each zinc finger can recognize and attach to a specific type of DNA; the more zinc fingers, the more DNA that can be recognized. Zimmerman designs these proteins to attach to specific DNA combinations-namely, the cccDNA that is the culprit behind chronic hepatitis B infections.
"Because we know the DNA sequence of hep B virus, we can decide what sequence of zinc finger protein is needed to bind it," says Zimmerman. She explains that the concept is similar in principle to the Denver boot, a type of wheel clamp used by some police departments to immobilize illegally parked vehicles. When a Denver boot is placed on a wheel, the car can't go anywhere. "The idea is that these zinc finger proteins are the clamp, and that particular form of hep B virus in the liver is the tire."
Once she was convinced that the proteins were attaching well to their targets, Zimmerman tried the process in a model of a hepatitis B infection to see how it affected production of the virus. And sure enough, she found that the proteins travelled to the hepatitis B DNA and bonded to it strongly, preventing the DNA from reproducing the hepatitis B virus. The next step is to determine whether the zinc finger proteins can make the DNA break down and disappear.
In September, Zimmerman filed a patent for the application of zinc finger proteins as future treatments. "The proteins are the first therapeutic to target cccDNA," she says. "We've seen very good results so far with inhibition of the virus, and it's exciting to take the next step."