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Genetic editing cures hemophilia

Doctors have for the first time been able to treat hemophilia by a process called gene editing – reparing flaws in the genetic code of a living animal.

The team, from the Center for Cellular and Molecular Therapeutics (CCMT) at the Children’s Hospital of Philadelphia, calls it a breakthrough in progress towards being able to treat a wide range of genetic diseases.

The researchers used two versions of a genetically engineered virus called adeno-associated virus, or AAV. One version carried enzymes that cut DNA in an exact spot, with the other carrying a replacement gene to be copied into the DNA sequence. The researchers did this using the liver cells of living mice.

“Our research raises the possibility that genome editing can correct a genetic defect at a clinically meaningful level after in vivo delivery of the zinc finger nucleases,” says study leader, Katherine A High.

The technique makes use of genetically engineered enzymes called zinc finger nucleases (ZFNs), which can edit mutated sequences of DNA.

By designing ZFNs custom-matched for the factor 9 gene (F9) and using them in conjunction with a DNA sequence, the team was able to restore normal gene function lost in hemophilia.

The mice that received the ZFN/gene combination produced enough clotting factor to reduce blood clotting times to nearly normal levels.  The improvements persisted over the eight months of the study, and showed no toxic effects on growth, weight gain or liver function.

“We established a proof of concept that we can perform genome editing in vivo, to produce stable and clinically meaningful results,” says High. “We need to perform further studies to translate this finding into safe, effective treatments for hemophilia and other single-gene diseases in humans, but this is a promising strategy for gene therapy.”

Conventional gene therapy techniques suffer from the problem that they can randomly deliver a replacement gene into an unfavorable location, bypassing the normal biological regulatory components controlling the gene.

This imprecise targeting carries a risk of what’s known as insertional mutagenesis, in which the corrective gene causes an unexpected alteration, such as triggering leukemia. Because ZFNs can precisely target a specific site along a chromosome, this danger could now be eliminated.