Table 4.
Gene editing studies in hemophilia
| Gene targeted | Cell type | Gene editing | Nuclease delivery | Donor | Results in recipient model |
|---|---|---|---|---|---|
| Hemophilia B | |||||
| F949 Li, 2011 |
Hepatocytes | Gene correction | ZFN via plasmid and AAV delivery system | DNA | Correction of FIX in neonatal HB mouse model |
| F950 Anguela, 2013 |
Hepatocytes | Gene correction | ZFN via plasmid and AAV delivery system | DNA | Correction of FIX in adult HB mouse model |
| F951 Lyu, 2018 |
iPSCs | Gene addition | Cas9 via plasmid electroporation | Plasmid | FIX secreted in transplanted HB mouse |
| F952 Ramaswamy, 2018 |
iPSCs | Gene addition | Cas 9 plasmid nucleofection | DNA | Correction of FIX in HLCs in HB mouse |
| F9353 Morishige, 2020 |
iPSCs | Gene correction | Cas9 plasmid nucleofection | DNA | Detection of transfected HLCs in HB mouse |
| F954 Stephens, 2019 |
Stem cells | Gene addition | Cas9 plasmid and Ad platform | Plasmid | Correction of FIX in HB mice |
| F955 Wang, 2020 |
Hepatocytes | Gene addition | Cas9 plasmid and AAV delivery system | Plasmid | Correction of FIX in adult and neonatal HB mice |
| F956 Ma, 2022 |
ESCs | Gene addition | Cas9 plasmid electroporation | Plasmid | Detection of FIX at the RNA and protein levels |
| F957 Lee, 2022 |
Hepatocyte | Gene addition | Cas9 plasmid and AAV delivery system | Plasmid | Detection of FIX in HB mouse model |
| F958 He, 2022 |
Hepatocyte | Gene addition | Cas9 plasmid and AAV delivery system | Plasmid | Correction of FIX in adult and neonatal HB mice |
| Hemophilia A | |||||
| F959 Sharma, 2015 |
Hepatocytes | Gene correction | ZFN via plasmid and AAV delivery system | DNA | Correction of FVIII in HA mouse model |
| F860 Park, 2015 |
iPSCs | Gene correction | Cas9 via plasmid electroporation | None | FVIII activity restored in HA mouse model |
| F861 Hu, 2019 |
iPSCs | Gene correction | Cas9 via plasmid nucleofection | ssODNs | FVIII activity restored in HA mouse model |
| F862 Park, 2019 |
iPSCs | Gene addition | Cas9 via RNP electroporation | DNA | FVIII secreted in the iPSCs of patients with HA |
| F863 Sung, 2019 |
iPSCs | Gene addition | Cas9 via plasmid electroporation | Plasmid | FVIII secreted in the iPSCs of patients with HA |
| F864 Chen, 2019 |
Hepatocytes | Gene addition | Cas9 via plasmid and AAV delivery system | Plasmid | FVIII secreted in HA mouse hepatocytes |
| F865 Zhang, 2019 |
Hepatocytes | Gene addition | Cas9 via plasmid and AAV delivery system | Plasmid | FVIII secreted in HA mouse hepatocytes |
| F866 Ramamurthy, 2021 |
Placental cells | Gene addition | Cas9 via plasmid delivery system | Plasmid | FVIII secreted in human placental cells |
| F867 Cho, 2021 |
iPSCs | Gene correction | Cas9 via plasmid delivery system | Plasmid | FVIII secreted in the iPSCs of patients with HA |
| F868 Hu, 2023 |
iPSCs | Gene correction | Cas9 via plasmid delivery system | Plasmid | FVIII secreted in the iPSCs of patients with HA |
Ad, adenoviral vector; ESCs, embryonic stem cells; RNP, ribonucleoprotein; ssODNs, single-stranded oligodeoxynucleotides.