Gene editing success for haemophilia

Scientists have, for the first time, successfully treated a blood disorder by repairing errors in the DNA of a living animal.

Researchers from the Children's Hospital of Philadelphia, together with California-based Sangamo BioSciences, have applied an innovative genome editing technique to treat haemophilia B, which affects around one in 30,000 boys and men.

The team, led by Dr Katherine High, tested their methods using mice genetically engineered to carry a defective human gene called F9, which causes them to develop the blood clotting disease.

Usually when you cut yourself a group of proteins will move to site of injury and combine with platelets in the blood to form a protective scab. People with errors in the F9 gene lack one of these proteins, factor IX, which prevents them from forming blood clots properly.

When the researchers replaced the faulty F9 gene with a fully functional version in affected liver cells of the mice they found that blood clotting was restored to nearly normal levels.

Until now, genome editing has required cells to be removed from the patient's body before they can be genetically altered - an approach which is unfeasible for treating many human genetic disorders. In this study, published in the journal Nature, the group managed to use the cell's own repair machinery to replace the faulty gene without having to remove it from the body at all.

'We established a proof of concept that we can perform genome editing in vivo, to produce stable and clinically meaningful results', said Dr High. 'We need to perform further studies to translate this finding into safe, effective treatments... but this is a promising strategy for gene therapy'.

DNA cleaving tools called zinc-finger nucleases (ZFNs) were designed to specifically target and remove the dysfunctional F9 gene. These were injected into the abdomen of a two-day old mouse, along with a corrected copy of the F9 DNA sequence, in a harmless virus case, which heads straight to the liver. There, the ZFNs cut out the faulty gene, triggering the cell's DNA repair machinery to incorporate the correct version instead.

At five-weeks-old the level of factor IX in the blood had increased by 3-7 percent in treated mice, compared to controls, which was enough to cause a significant improvement in clotting function. Importantly, this genetic modification was demonstrated to be a permanent change in the treated mice's liver cells.

'In theory, almost all genetic diseases could be amenable to this type of treatment', Professor Mark Kay, a gene therapy researcher at Stanford University in California, told Nature News. He added, however, that 'there are still some technical hurdles that have to be overcome before this is going to be a wide-scale medical therapy'.