In this project we have shown that the I22I inversion mutation which is the underlying cause of half of all hemophilia A cases can be corrected using our novel genome editing approach. Using this approach, we successfully replaced the portion of the Factor 8 that is missing in these patients. We showed successful editing of the Factor 8 gene in human cells and correction of the inversion mutation in patient derived cells. We found that the corrected Factor 8 gene directs the expression of the full length Factor VIII clotting factor which should restore clotting activity in I22I hemophilia patients. Since the correction of the I22I mutation is performed at the level of the genome, it is expected to be permanent and last for the life of the patient, unlike current gene therapy approaches. In addition, unlike most genome editing platforms used currently, our editing approach does not require prior cutting of the genome, thus significantly safer as it reduces the likelihood of generating new mutations during the process of genome editing. We expect to develop this safe and novel genome editing approach for clinical genome editing for the cure of I22I hemophilia A.