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Gene editing success for haemophilia

11 July 2011
Appeared in BioNews 615

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'.



Cut-and-paste therapy fixes mouse haemophilia
Nature News |  26 June 2011
Doctors make breakthrough in repairing genetic defects
Guardian |  26 June 2011
Gene Editing Treats Blood Disease
The Scientist |  27 June 2011
Genome Editing, A Next Step in Genetic Therapy, Corrects Hemophilia in Animals
Children's Hospital of Philadelphia press release |  27 June 2011
Hemophilia Is Target of Therapy on Genome
New York Times |  27 June 2011
In vivo genome editing restores haemostasis in a mouse model of haemophilia
Nature |  26 June 2011
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11 December 2017 - by Charlotte Spicer 
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2 February 2015 - by Dr Lucy Freem 
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15 December 2014 - by Sean Byrne 
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A gene therapy technique that repairs faulty genes by 'editing' their DNA could lead to new treatments for inherited blood disorders and HIV, say US researchers. The approach could help address safety concerns over current gene therapy methods, many of which rely on specially adapted viruses to deliver working genes...
7 June 2004 - by BioNews 
A US biotechnology firm announced last week that it is discontinuing its haemophilia trial, citing technical and safety reasons. Avigen said that it was stopping the trial so it could concentrate on neurological diseases, but it also said that the gene therapy treatment for haemophilia faced 'certain scientific, regulatory and...
18 February 2002 - by BioNews 
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11 June 2001 - by BioNews 
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6 March 2000 - by BioNews 
Two patients in a gene therapy trial for haemophilia, a blood-clotting disorder, have shown a marked improvement in their condition. The US team, from Stanford University School of Medicine and the Children's Hospital of Philadelphia, admit they were surprised by the results, which are published in this month's Nature Genetics...
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