Researchers at the University of Alabama at Birmingham (UAB) have developed a modified poliovirus, incapable of transmitting the disease, to deliver genes specifically to motor neurons in the spinal cord. (Nature Biotechnology, 9-00)
University of Alabama at Birmingham
August 25, 2000
Contact: Joy Carter
BIRMINGHAM, Ala. -- Researchers at the University of Alabama at Birmingham (UAB) have developed a modified poliovirus, incapable of transmitting the disease, to deliver genes specifically to motor neurons in the spinal cord. "The technology may provide a new approach to treating spinal cord injuries and neurological diseases," according to lead investigator Casey D. Morrow, Ph.D., professor of microbiology at UAB. Details of the study will be published in the September issue of "Nature Biotechnology."
"This is the first time that a poliovirus-based delivery system, called a replicon, has been used to target motor neurons," says Morrow. Motor neurons are the cells within the spinal cord that are responsible for movement and are the natural targets for poliovirus. "We have modified the virus by deleting the genes necessary for it to cause polio, while leaving intact its ability to target motor neurons. This gives us a vehicle for delivering potentially beneficial genes directly to the spinal cord."
In the first phase of the study, researchers added a green fluorescent protein to the modified poliovirus to test its effect. "It showed that we could safely deliver the protein directly to the motor neurons and that the motor neurons would express the effects of the protein for a short period of time without causing damage," says Morrow. "The system seems to mimic very closely how neurological proteins are expressed in nature -- for a short period of time in a localized area."
In the second phase, researchers modified the poliovirus using Tumor Necrosis Factor (TNF), a protein known to have a myriad of effects on the central nervous system, and tested it in spinal cords of mice. "The TNF was expressed and biologically active, as evidenced by the effects on the motor neurons and surrounding cells," says Morrow. "That is important. It demonstrates that we may be able to use the system to deliver beneficial genes, such as nerve growth factor, to repair or restore damaged motor neurons."
In ongoing studies, researchers are now using the system to test whether it can be used to repair damaged motor neurons. "With spinal cord injury, impact and initial swelling result in damage to motor neurons," says Morrow. "The delivery system could be used at this point to deliver protein molecules that would suppress swelling or allow an anti-inflammatory response. The other potential is that the system may be used to deliver molecules that would support neuron re-growth."
The research is a collaborative effort between UAB and Replicon Technologies Inc., a Birmingham-based biotechnology company that is commercializing the technology developed in Morrow's laboratory. "UAB has provided an excellent environment for the development and application of this novel approach," says Morrow. "The research team represents many different disciplines that all bring important expertise to the table."
Other investigators involved in the study are Andrea Bledsoe, UAB graduate student with the department of microbiology; Cheryl Jackson, UAB research assistant with the department of physiological optics; and Sylvia McPherson, UAB research core facility, assistant director with the Center for AIDS Research.
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