New Technique Adds Precision And Permanence To Gene Therapy

"To date gene therapy has relied upon vectors that randomly insertgenes into the cell's genome," explains Savio L. C. Woo, PhD, Professorand Chairman of Gene and Cell Medicine at Mount Sinai School ofMedicine and corresponding author on the study. "The technique wedeveloped identifies a specific sequence which only occurs in a fewplaces in the mammalian genome. These sequences occur between genes sothere is no danger of the insertion of the gene damaging existing genesin the cell.

"Because the genes are inserted permanently, a few applications wouldsuffice to permanently correct a disease." Dr. Woo and his colleague LiChen , PhD, a post-doctoral fellow at Mount Sinai) were able to curePKU in mice with just three intravenous injections. The levels ofphenylalanine in the treated mice dropped to normal range and remainedstable thereafter. Their fur color also changed from gray to black,indicating that they were now producing normal levels of melanin, apigmentation which is under-produced in mice and humans with PKU.

Drs. Woo and Chen used a gene from a bacteriophage that recognizes aspecific DNA sequence. This sequence occurs only several times in theentire mouse genome and it is always found in the non-coding regionbetween genes. Similar sequences are found in a few locations in thehuman genome that are also between existing genes.

"The current challenge is to identify a suitable means of introducingDNA into liver cells," said Dr. Woo. "Once that technology isdeveloped, this new technique will provide a safe and efficient meansof integrating the DNA into the cell's genome."

In addition to PKU, this technique could be used to cure other geneticdiseases caused by missing liver enzymes including hemophilia and ureacycle enzyme deficiencies, as well as cholesterol clearing from theblood and others.