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.