In a cell, RNA is copied from a strand of DNA; it serves as the messenger that conveys DNA's genetic instructions to the cell's cytoplasm, where proteins are made. In retinitis pigmentosa, a mutant gene calls for the creation of a protein that damages the eye's light-sensitive rod cells.
About 40 percent of people with retinitis pigmentosa have the "autosomal-dominant" form; that is, they inherited a defective gene from one parent who has the disease, but also received a normal gene copy from the other parent. (About half the cases of retinitis pigmentosa occur with no known family history.)
The UF research targets the autosomal-dominant form of the disease in rats.
"We designed a ribozyme to cut up the messenger RNA that have the copies of the bad gene, while leaving alone the copies of the good gene," Lewin said.
The genes themselves--good and bad--are not disturbed.
The designer ribozyme was injected into lab rats, which were bred by a University of California School of Medicine team to have a disease similar to human retinitis pigmentosa. The California research team was led by Matthew LaVail and John Flannery. Hauswirth developed the viral tool for delivering the ribozyme to the eye.
"We have seen significant protection of the eye cells three months after injecting the ribozymes. That's a long time in a rodent's life," Lewin said. "We're now working to see if the protection lasts for six months."
Additional studies will be conducted in pigs, which can provide an even closer match to the human eye.
Over time, ribozymes may be developed to fight other autosomal dominant diseases, including Marfan syndrome, a genetic disorder of the connective tissue, and some forms of ALS, more commonly known as Lou Gehrig's disease.
"As long as you can design a ribozyme that could block the expression of the mutant gene, this approach ought to work," Lewin said.