Manipulating Ribozymes to Control Gene Activity

A new study explores the use of ribozymes--catalytic RNA that cleaves certain target RNA and thus prohibits gene function--in conjunction with specific drugs to control gene expression as a possible treatment for chronic diseases.

Investigators at Harvard Medical School (Boston, MA, USA) evaluated hundreds of known ribozymes and found two that functioned well in human cells. When the ribozymes were inserted into cells, they shut down gene activity by cleaving RNA and preventing protein synthesis. Next, the investigators searched for drugs that would inhibit ribozyme activity and allow the gene to continue to function. Two likely candidates were found.


To demonstrate how the system could function, the investigators inserted the gene for luciferase along with an embedded ribozyme into the retinas of mice. With no treatment, luciferase was not produced, but after treatment with a ribozyme inhibitor, luciferase could be detected. These findings were published in the September 23, 2004, issue of Nature.

"Perhaps the most exciting aspect of the new work is that, in conjunction with other technologies, we will likely be able to ‘tailor' gene regulation systems to respond to any drug or chemical,” said senior author Dr. Richard Mulligan, professor of genetics at Harvard Medical School. "Ultimately, the system should also enable the ‘release' of a therapeutically useful protein in response to changing concentrations of chemicals in cells. For instance, it may be possible to develop a gene therapy whereby cells are engineered to secrete insulin in response to a rise in glucose. Such ‘biological sensing' could have a wide range of applications.”



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