New gene therapy technique cures PKU
made a breakthrough after it was revealed that the method had cured
phenylketonuria (PKU) in mice.
The method is a potential breakthrough in the application of gene therapy that despite the media spotlight is still at a relatively immature stage of development. News that this technique has effectively cured a serious disease, albeit in mice, has raised possibilities as well as expectations.
In addition to PKU, this technique could be used to cure other genetic diseases caused by missing liver enzymes including haemophilia and urea cycle enzyme deficiencies, as well as cholesterol clearing from the blood and others.
"To date gene therapy has relied upon vectors that randomly insert genes into the cell's genome," said Savio Woo, professor and chairman of Gene and Cell Medicine at Mount Sinai School of Medicine and author on the study.
"The technique we developed identifies a specific sequence which only occurs in a few places in the mammalian genome. These sequences occur between genes so there is no danger of the insertion of the gene damaging existing genes in the cell."
The technique involves inserting genes into non-coding regions of the genome so there is no danger of interfering with the functioning of other genes. Once inserted, the gene remains a permanent part of the cell's genome.
Dr Woo and his colleague Li Chen used a gene from a bacteriophage that recognises a specific DNA sequence.
This sequence occurs only several times in the entire mouse genome and it is always found in the non-coding region between genes.
Similar sequences are found in a few locations in the human genome that are also between existing genes.
Woo and Chen were able to cure PKU in mice with just three intravenous injections. The levels of phenylalanine in the treated mice dropped to normal range and remained stable thereafter.
Their fur colour also changed from grey to black, indicating that they were now producing normal levels of melanin, a pigment, which is under-produced in mice and humans with PKU.
"Because the genes are inserted permanently, a few applications would suffice to permanently correct a disease," said Woo.
"The current challenge is to identify a suitable means of introducing DNA into liver cells. Once that technology is developed, this new technique will provide a safe and efficient means of integrating the DNA into the cell's genome."
Phenylketonuria is one of the commonest inherited disorders, occurring in approximately 1 in 10,000 babies born in the US. It occurs in babies who inherit two mutant genes for the enzyme phenylalanine hydroxylase (PAH).
This enzyme normally breaks down molecules of the amino acid phenylalanine that are in excess of the body's needs for protein synthesis.
Woo and Chen's study appears in this week's edition of PNAS.
