New Tools to Tackle Genetic Flaws

The Rochester team used a synthetic molecule - called an antisense morpholino oligonucleotide - that mimics a segment of the genetic code. In this case the morpholino was specifically designed to bind to the toxic RNA and neutralize its harmful effects by releasing the captured proteins. When injected into the muscle cells of mice with myotonic dystrophy the molecule found its way to the cell nucleus, broke up the deposits of toxic RNA, freed the captive muscleblind proteins, and ultimately improved the function of the muscle cells.

The researchers specifically observed a restoration of proper electrical control in the cells, which is a convenient way to monitor the condition. However, because the hostage proteins play a role in a myriad of other cellular functions, they believe that this treatment will ultimately alleviate other aspects of the disease as well.

"Based on our current understanding we would predict that by releasing the proteins held hostage, many of the symptoms of the disease may potentially be corrected by this approach," said URMC neurologist Thurman Wheeler, M.D., co-author of the study.

These genetic tools are relatively new and have provided researchers with a heretofore unprecedented ways to precisely target and manipulate genetic activity. "The current textbooks for medical students do not have chapters on antisense oligonucleotides, but this will change in the near future," said Thornton. "As compared to conventional drugs that work on proteins, antisense oligonucleotides work on RNA. They have been around for 20 years, but only recently is their full potential being realized. They provide great flexibility and they can be developed rapidly."

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