Gene therapy corrects PKU in mice

“NEW YORK (Reuters Health) – Researchers have used a novel gene transfer technique to remedy a genetic defect, phenylketonuria (PKU), in mice. The process targets a corrective gene to a specific neutral site on the chromosomes of liver cells, so that inserting the gene doesn’t cause any genetic damage
PKU is an inherited metabolic disorder that predisposes affected children to severe and irreversible mental retardation. PKU is caused by a deficiency of the liver enzyme PAH, which converts phenylalanine to tyrosine.
In mice with PKU, site-specific delivery of a new PAH gene to the liver led to complete and long-lasting correction of the condition, Dr. Savio L. Woo, director of the Institute for Gene Therapy at Mount Sinai School of Medicine in New York and past president of the American Society for Gene Therapy told Reuters Health.
“The PKU mice became normal and lost all their symptoms,” Woo said. He presented his team’s findings in St. Louis at the annual meeting of the American Society of Gene Therapy.
“What we’ve learned is that we could utilize an enzyme that is made by bacteria to deliver via injection into the blood the corrective gene into neutral spots of mouse and human chromosomes of cells so they do not cause cancer,” Woo explained. “Once the gene integrates, it corrects the genetic defect.”
With other gene delivery techniques, genes are inserted randomly in the DNA of target cells, with the risk of damaging chromosomes.
Moreover, the bacterial enzyme system of gene delivery contains no viral component “which is another advantage because we don’t have to deal with any untoward consequences of viruses,” Woo said.
The researchers believe their method of gene transfer can potentially be developed for a multitude of genetic disorders.
“However, translation into humans is going to take time,” Woo cautioned, noting that “the current method is too toxic for people.”
Nonetheless, he said, “it’s almost like we are just one step away from providing major cures for these kinds of genetic diseases — anything that is manifested in the liver we can possibly treat with this system.”