3.5. Genome editing
The most advanced approach to genome editing in haemophilia is usage of zinc finger nuclease (ZFN). There have been several recent orphan designations of products with this alternative approach to overcoming the defective gene. The gene editing technique can correct the endogenous genetic defect or direct the integration site of a therapeutic gene through nuclease-targeted double-strand DNA breaks and homology-directed repair. Thus, gene-editing technologies are based on harnessing the natural repair machinery of the cell to modify DNA. A phase 1 study (NCT02695160) is currently recruiting using AAV-directed correction using ZFN targeted insertion of FIX gene into the first intron of the albumin locus. Although gene editing holds significant promise for haemophilia, in its current state, the approach still requires AAV for delivery of the nuclease or transgene [29]. Therefore, the same limitations for AAV gene therapy are present for gene-editing approaches.