Table 4.
Selected early ex vivo gene therapy trials with genome editors.
| Nuclease | Target gene and effect | Disease | Sponsor organization | Country | NCT number | Date posted |
|---|---|---|---|---|---|---|
| ZFN | CCR5 knockout | HIV-1 | University of Pennsylvania | USA | NCT00842634 | 2009 Feb |
| ZFN | CCR5 knockout | HIV-1 | Sangamo Biosciences | USA | NCT01044654 | 2010 Jan |
| ZFN | CCR5 knockout | HIV-1 | Sangamo Biosciences | USA | NCT01252641 | 2010 Dec |
| ZFN | CCR5 knockout | HIV-1 | Sangamo Biosciences | USA | NCT01543152 | 2012 Mar |
| ZFN | CCR5 knockout | HIV-1 | Sangamo Biosciences | USA | NCT02225665 | 2014 Aug |
| ZFN | CCR5 knockout | HIV-1 | University of Pennsylvania | USA | NCT02388594 | 2015 Mar |
| ZFN | CCR5 knockout | HIV-1 | City of Hope Medical Center | USA | NCT02500849 | 2015 Jul |
| ZFN | Disrupt BCL11A | β-thalassemia | Sangamo Biosciences | USA | NCT03432364 | 2018 Feb |
| ZFN | CCR5 knockout | HIV-1 | University of Pennsylvania | USA | NCT03617198 | 2018 Aug |
| ZFN | Disrupt BCL11A | SCD | Bioverativ | USA | NCT03653247 | 2018 Aug |
| ZFN | CCR5 knockout | HIV-1 | Case Western Reserve University | USA | NCT03666871 | 2018 Sep |
| TALEN |
TCRα, TCRβ, CD52 knockout; Create universal T-cells |
Advanced lymphoid malignancy | Institut de Recherches Internationales Servier |
UK, USA France |
NCT02746952 | 2016 Apr |
| TALEN |
TCRα, TCRβ, CD52 knockout; Create universal T-cells |
Refractory B-ALL | Institut de Recherches Internationales Servier |
UK, Belgium, France, USA |
NCT02808442 | 2016 Jun |
| TALEN | PD-1 and CD52 knockout | AML | Cellectis S.A. | USA | NCT03190278 | 2017 Jun |
| TALEN | PD-1 and CD52 knockout | AML | Cellectis S.A. | USA | NCT04106076 | 2019 Sep |
| TALEN | PD-1 and CD52 knockout | Multiple myeloma | Cellectis S.A. | USA | NCT04142619 | 2019 Oct |
| TALEN | PD-1 and CD52 knockout | CD22+ B cell acute lymphoblastic leukemia | Cellectis S.A. | USA | NCT04150497 | 2019 Nov |
| Cas9 | PD-1 knockout | Metastatic non-small cell lung cancer | West China Hospital, Sichuan University | China | NCT02793856 | 2016 Jun |
| Cas9 |
TCRα, TCRβ, B2M knockout; Create universal T-cells |
B-cell leukemia | Chinese PLA General Hospital |
China | NCT03166878 | 2017 May |
| Cas9 | CCR5 knockout | HIV-1 | Affiliated Hospital to Academy of Military Medical Sciences |
China | NCT03164135 | 2017 May |
| Cas9 | TCRα, TCRβ, PD-1 knockout | Various malignancies | University of Pennsylvania | USA | NCT03399448 | 2018 Jan |
| Cas9 | Disrupt BCL11A | β-thalassemia | CRISPR Therapeutics | UK, Germany | NCT03655678 | 2018 Aug |
| Cas9 | Disrupt BCL11A | SCD | Vertex Pharmaceuticals Incorporated and CRISPR Therapeutics |
USA | NCT03745287 | 2018 Nov |
| Cas9 | CISH knockout | Metastatic gastrointestinal epithelial cancer | National Cancer Institute | USA | NCT03538613 | 2018 May |
| Cas9 | CISH knockout | Metastatic gastrointestinal epithelial cancer | Masonic Cancer Center, University of Minnesota |
USA | NCT04089891 | 2019 Sep |
| TALEN |
TCRα, TCRβ, CD52 knockout; create universal T cells (15-year follow-up study) |
Advanced lymphoid malignancy | Institut de Recherches Internationales Servier |
UK, Belgium, France, USA |
NCT02735083 | 2016 Apr |
| Cas9 | Disrupt BCL11A (15-year follow-up study) |
β-thalassemia and severe SCD | Vertex Pharmaceuticals Incorporated and CRISPR Therapeutics | USA, UK, Germany |
NCT04208529 | 2019 Nov |
PD-1: programmed cell death protein 1; CISH: cytokine-induced SH2 protein; B2M: β-2 microglobin.