Table 3.
Overview of HSC-based clinical studies using gene editing.
| NCT Number | Strategy | Phase | Country | Target/Modification | Nuclease | Delivery | Industry Sponsorship/Sponsor |
|---|---|---|---|---|---|---|---|
| β-Thalassemia | |||||||
| NCT03655678 | Ex vivo | I/II | Germany (Canada, Europe) | Autologous CD34+ HSPCs modified at the enhancer of the BCL11A | CRISPR/Cas9 | RNP electroporation | CRISPR Therapeutics (Vertex Pharmaceuticals Incorporated) |
| NCT03728322 | Ex vivo | I | HBB gene correction in patient specific iHSCs | CRISPR/Cas9 | Not Specified | Allife Medical Science and Technology Co., Ltd. | |
| NCT03432364 | Ex vivo | I/II | USA | CD34+ HSPCs | ZFN | mRNA | Sangamo Therapeutics |
| Sickle Cell Disease | |||||||
| NCT03653247 | Ex vivo | I/II | USA (USA, Europe) | Autologous CD34+ HSPCs modified at the BCL11A erythroid enhancer | ZFN | mRNA | Rioverativ, a Sanofi company |
| NCT03745287 | Ex vivo | I/II | USA (USA, Europe) | Autologous CD34+ HSPCs modified at the BCL11A erythroid enhancer | CRISPR/Cas9 | RNP | CRISPR Therapeutics (Vertex Pharmaceuticals Incorporated) |
| NCT04443907 | Ex vivo | I/II | USA | Autologous CD34+ HSPCs modified at the BCL11A erythroid enhancer | CRISPR/Cas9 | RNP | Novartis Pharmaceuticals (Novartis Pharmaceuticals & Intellia Therapeutics) |
| NCT04774536 | Ex vivo | I/II | USA | Autologous CD34+ HSPCs | CRISPR/Cas9 | RNP/ssODN electroporation | University of California (Los Angeles), University of California (Berkeley) |
| NCT04853576 | Ex vivo | I/II | USA | HBG1/2 promoter | CRISPR/Cas12 | RNP | Editas Medicine |
| Mucopolysaccharidosis I | |||||||
| NCT02702115 | In vivo | I/II | USA | Insertion of corrected copy of α-L-iduronidase gene into the Albumin locus | ZFN | AAV | Sangamo Therapeutics |
| Mucopolysaccharidosis II | |||||||
| NCT03041324 | In vivo | I/II | USA | Insertion of corrected copy of α-L-iduronidase gene into the Albumin locus | ZFN | AAV | Sangamo Therapeutics |
| Hemophilia B | |||||||
| NCT02695160 | In vivo | I | USA, Europe | Insertion of corrected copy of the factor 9 gene into the Albumin locus | ZFN | AAV | Sangamo Therapeutics |
| HIV AIDS | |||||||
| NCT02500849 | Ex vivo | I | USA | Disruption in CD34+ HSPCs of CD4 co-receptor gene, CCR5 | ZFN | mRNA electroporation | City of Hope Medical Center, Sangamo Therapeutics, California Institute for Regenerative Medicine |
| NCT03164135 | Ex vivo | - | China | Disruption in CD34+ HSPCs of CD4 co-receptor gene, CCR5 | CRISPR/Cas9 | RNP | Academy of Military Medical Sciences, Peking University, Capital Medical University |
Abbreviations: AAV—adeno-associated virus; RNP—ribonucleoprotein; ZFN—zinc finger nuclease.