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Gene Therapy Technique for Inherited Heart Problems in The Pipeline

e transfer,’ said Byrne, who also is affiliated with the UF Genetics Institute. ‘We're using the very same strategies used with medical treatment but without ongoing use of medications.’ In evaluating methods of delivering the genes, UF researchers compared three subtypes of the adeno-associated virus, or AAV, which is not known to cause disease and does not appear to trigger a major immune system reaction. They tested the ability of AAV-1, AAV-8 and AAV-9 to insert genes into skeletal and heart muscle in newborn and in adult mice.

Tests revealed that AAV-9 was taken up throughout the heart muscle at 200 times the levels achieved with AAV-1. In contrast, AAV-8 was taken up by heart muscle at 20 times the levels achieved with AAV-1, though it was less precise, also delivering a significant amount of its genetic payload to the liver and to other muscles. Because AAV-9 was so readily taken up by cells, a lower dose likely could be used to achieve a therapeutic effect in people, Byrne said. It also has a unique outer shell that helps it break through blood vessel walls so it can be readily taken up by cells requiring repair. The scientists also modified AAV-9 to contain copies of a therapeutic gene that pumps out an enzyme missing in a mouse model for Pompe disease. The ailment is caused by a single defective gene that fails to produce adequate levels of an enzyme that normally breaks down the carbohydrate glycogen, used to store energy. The disease causes gradual weakening of muscle and heart tissue when glycogen accumulates in muscles, limiting their ability to contract.

‘This is a way of delivering gene therapy to the heart that is aimed at treating genetic diseases affecting the heart,’ Byrne said. ‘It's efficient and long lasting. One of the other distinguishing features of our research is it's probably the first to demonstrate a physiologic correction of a genetic cardiac abnormality.’ Additional tests in rhesus monkeys conducted in conjunction
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