Hemophilia A (HA) is the most commonly occurring inheritable deficiency of blood coagulation. Severely affected individuals suffer frequent spontaneous haemorrhaging, which can lead to chronic painful and debilitating arthropathies, hematomas, and potentially life-threatening internal bleeding. About 50% of severe HA cases are caused by large gene inversions between inverted repeats surrounding the F8 gene.
In an attempt to find novel ways to flawlessly revert these gene defects, The Buchholz laboratory has developed a recombinase-based system to correct a 140 kb genomic inversion of the F8 gene causing severe Hemophilia A. The team was able to reverse the defect in patient derived cells at high efficiency, indicating that this approach might be suitable to develop a curative therapy for patients carrying this genetic inversion.