By using a technique called genome editing, scientists have successfully treated the genetic blood clotting disorder, hemophilia, in mice. These results raise the possibility of using gene therapy techniques to treat a wider range of genetic diseases in humans.

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In this study, Katherine High of the Children's Hospital Philadelphia, PA, and colleagues used mice that were genetically engineered to carry a faulty version of the human gene F9, which is found in people with hemophilia (Nature doi:10.1038/ nature10177; published online 26 June 2011). F9 helps control the level of blood coagulation factor IX. The circulating levels of factor IX in most individuals with hemophilia are less than 1% of the levels of factor IX in unaffected individuals. The genetically engineered mice in this study had no detectable factor IX. High and her colleagues worked with a team at Sangamo BioSciences in Richmond, CA, to develop enzymes called zinc-finger nucleases that would target and remove the portion of the F9 gene containing 95% of F9 mutations.

The research team injected an engineered viral vector carrying the zinc-finger nucleases and another viral vector containing the wild-type F9 sequence into mice. Both of these vectors were designed to travel to the liver. After treatment, the circulating levels of factor IX ranged from 3–7% of normal levels. Additionally, the average clotting time for mice that received the treatment was 44 seconds, which did not differ significantly from the average clotting time (36 seconds) for wild-type mice. The mice with hemophilia had average clotting times of 67 seconds.

When the researchers partially removed the livers of mice that had received the treatment, factor IX was still produced at similar levels, showing that the genome edits persisted with the division of cells. Administration of the treatment to both wild-type and hemophiliac mice appeared to have no effects on weight gain or growth in these mice. Additionally, follow-up tests at 4, 29 and 32 weeks after injection showed that there were no changes in the liver function of treated mice.

Previous studies have shown that zinc-finger nucleases can be used to effectively target specific genes in cells that have been isolated and removed from the body. This study, however, represents the first time that zinc-finger nucleases have been shown to work in vivo. These results open up the possibility of using zinc-finger nucleases to treat hemophilia and other genetic diseases that affect cells that cannot be easily removed from the body.