Coaxing Cells to Read Through Genetic Mistakes
Could Provide New Gene Therapy Strategy

Researchers at the University of Western Australia in Perth and Hammersmith Hospital in London have developed a new gene correction strategy in mice with Duchenne muscular dystrophy that could someday be used to treat that disease and possibly other genetic disorders.

MDA grantee Stephen Wilton in Perth was part of the research team, which published results in the Jan. 2 issue of Proceedings of the National Academy of Sciences.

The team didn't insert any new genes or use any viruses as genetic delivery vehicles. Instead, they injected chemicals called antisense oligoribonucleotides (AOs), linked to a fatlike substance, into the muscles of mice carrying a mutation in the dystrophin gene. The mutation makes the gene unable to produce dystrophin, a protein essential for healthy muscle cells. The type of mutation these mice have can also cause Duchenne dystrophy in humans.

The AOs, the researchers say, allowed the muscle cells to "skip over" the genetic mutation that would normally stop dystrophin production. The cells then produced dystrophin molecules that were slightly shorter than normal, but probably partially functional.

More animal studies are needed to assess the safety and effectiveness of the procedure, including experiments to examine how well the shorter dystrophin protein works and how long it lasts in the cells.

The effects of the AOs are similar to those of the drug gentamicin, which is being tested in clinical trials in people with Duchenne and limb-girdle muscular dystrophies who have certain types of genetic mutations. Like the AOs, gentamicin also changes the way cells interpret genetic instructions.