Table 1. Interventional trials with genome editors.
| Delivery vector | Nuclease | Phase | Target gene and effect | Disease | Ex vivo/in vivo | Intervention | Sponsor organization | Country | NCT number | Date posted |
|---|---|---|---|---|---|---|---|---|---|---|
| Adenoviral vectors | ZFN | I | CCR5 knockout | HIV | Ex vivo | Modified CD4+ T cells | University of Pennsylvania | U.S.A. | NCT00842634 | 2/12/2009 |
| ZFN | I | CCR5 knockout | HIV | Ex vivo | Modified CD4+ T cells | Sangamo Biosciences | U.S.A. | NCT01044654 | 1/8/2010 | |
| ZFN | I/II | CCR5 knockout | HIV | Ex vivo | Modified CD4+ T cells | Sangamo Biosciences | U.S.A. | NCT01252641 | 12/3/2010 | |
| ZFN | I/II | CCR5 knockout | HIV | Ex vivo | Modified CD4+ T cells | Sangamo Biosciences | U.S.A. | NCT01543152 | 3/2/2012 | |
| ZFN | I/II | CCR5 knockout | HIV | Ex vivo | Modified CD4+ T cells | Case Western Reserve University | U.S.A. | NCT03666871 | 9/12/2018 | |
| AAV vectors | ZFN | I | Factor IX addition al albumin locus | Hemophilia B | In vivo | ZFN-mediated addition of Factor IX gene to the albumin locus of hepatocytes | Sangamo Biosciences | U.S.A. | NCT02695160 | 3/1/2016 |
| ZFN | I | α-L-iduronidase (IDUA) addition at albumin locus | MPS type I | In vivo | ZFN-mediated addition of IDUA gene to the albumin locus of hepatocytes | Sangamo Biosciences | U.S.A. | NCT02702115 | 3/8/2016 | |
| ZFN | I | Iduronate 2-sulfatase (IDS) addition at albumin locus | MPS type II | In vivo | ZFN-mediated addition of IDS gene to the albumin locus of hepatocytes | Sangamo Biosciences | U.S.A. | NCT03041324 | 2/2/2017 | |
| Cas9 | I | Removal of alternative splice site in CEP290 | Leber congenital amaurosis 10 | In vivo | ZFN-mediated removal of intronic alternative splice site in retinal cells | Allergan and Editas Medicine, Inc. | U.S.A. | NCT03872479 | 3/13/2019 | |
| Electroporation (mRNA) | ZFN | I/II | CCR5 knockout | HIV | Ex vivo | Modified CD4+ T cells | Sangamo Biosciences | U.S.A. | NCT02225665 | 8/26/2014 |
| ZFN | I | CCR5 knockout | HIV | Ex vivo | Modified CD4+ T cells | University of Pennsylvania | U.S.A. | NCT02388594 | 3/17/2015 | |
| ZFN | I | CCR5 knockout | HIV | ex vivo | Modified CD34+ hematopoietic stem cells | City of Hope Medical Center | U.S.A. | NCT02500849 | 7/17/2015 | |
| ZFN | I/II | Disrupt the erythroid enhancer in B-cell lymphoma/leukemia 11A (BCL11A) | β-thalassemia | Ex vivo | Modified hematopoietic stem cells | Sangamo Biosciences | U.S.A. | NCT03432364 | 2/14/2018 | |
| ZFN | I | CCR5 knockout | HIV | Ex vivo | Modified T cells with ZFN-mediated CCR5 deletion as well as the addition of CD4 CAR receptor and modified CXCR4 expression | University of Pennsylvania | U.S.A. | NCT03617198 | 8/6/2018 | |
| ZFN | I/II | Disrupt B-cell lymphoma/leukemia 11A (BCL11A) | sickle cell anemia | Ex vivo | Modified hematopoietic stem cells | Bioverativ | U.S.A. | NCT03653247 | 8/31/2018 | |
| TALEN | I | TCRα, TCRβ, CD52 knockout | Advanced lymphoid malignancy | Ex vivo | CD19-CAR modified T cells with CAR delivered by lentivirus and TALEN knockout CD52 and TCR to create universal T cells | Institut de Recherches Internationales Servier | U.K., U.S.A., France | NCT02746952 | 4/21/2016 | |
| TALEN | I | TCRα, TCRβ, CD52 knockout | Refractory B-ALL | Ex vivo | CD19-CAR modified T cells with CAR delivered by lentivirus and TALEN knockout CD52 and TCR to create universal T-cells | Institut de Recherches Internationales Servier | U.K., Belgium, France, U.S.A. | NCT02808442 | 6/21/2016 | |
| TALEN | I | Programmed cell death 1 (PD-1) and CD52 knockout | Acute myeloid leukemia | Ex vivo | CD123-CAR modified T cells with CAR delivered by lentivirus and TALEN-mediated knockouts | Cellectis S.A. | U.S.A. | NCT03190278 | 6/16/2017 | |
| TALEN | I | Programmed cell death 1 (PD-1) and CD52 knockout | Blastic plasmacytoid dendritic cell neoplasm | Ex vivo | CD123-CAR modified T cells with CAR delivered by lentivirus and TALEN-mediated knockouts | Cellectis S.A. | U.S.A. | NCT03203369 | 6/29/2017 | |
| TALEN | I | Programmed cell death 1 (PD-1) and CD52 knockout | Acute myeloid leukemia | Ex vivo | CD123-CAR modified T cells with CAR delivered by lentivirus and TALEN-mediated knockouts | Cellectis S.A. | U.S.A. | NCT04106076 | 9/23/2019 | |
| TALEN | I | Programmed cell death 1 (PD-1) and CD52 knockout | Multiple myeloma | Ex vivo | CS-1-CAR modified T cells with CAR delivered by lentivirus and TALEN-mediated knockouts | Cellectis S.A. | U.S.A. | NCT04142619 | 10/29/2019 | |
| TALEN | I | Programmed cell death 1 (PD-1) and CD52 knockout | CD22+ B cell acute lymphoblastic leukemia | Ex vivo | CD22-CAR modified T cells with CAR delivered by lentivirus and TALEN-mediated knockouts | Cellectis S.A. | U.S.A. | NCT04150497 | 11/4/2019 | |
| Cas9 | I/II | βTCRα, TCRβ, β-2 microglobin (B2M) knockout | B-cell leukemia | Ex vivo | CD19-CAR modified T cells with CAR delivered by lentivirus and Cas9 knockout B2M and TCR to create universal T cells | Chinese PLA General Hospital | China | NCT03166878 | 5/25/2017 | |
| Cas9 | I | TCRα, TCRβ, PD-1 knockout | Various malignancies | Ex vivo | Modified T cells with Cas9-mediated deletions and lentiviral transduction of NY-ESO-1 targeted TCR | University of Pennsylvania | U.S.A. | NCT03399448 | 1/16/2018 | |
| Cas9 | I/II | Disruption of the erythroid enhancer to BCL11A gene | β-thalassemia | Ex vivo | Ex vivo modified hematopoietic stem cells | CRISPR Therapeutics | U.K., Germany | NCT03655678 | 8/31/2018 | |
| Cas9 | I/II | Disruption of the erythroid enhancer to BCL11A gene | Sickle cell anemia | Ex vivo | Ex vivo modified hematopoietic stem cells | Vertex Pharmaceuticals Incorporated and CRISPR Therapeutics | U.S.A. | NCT03745287 | 11/19/2018 | |
| Cas9 | I/II | Creation of a CD19-directed T cell | Refractory B-cell malignancies | Ex vivo | CD19-directed T-cell immunotherapy | CRISPR Therapeutics | U.S.A., Australia | NCT04035434 | 7/29/2019 | |
| Cas9 | I | disruption of HPK1 | refractory B cell malignancies | Ex vivo | CD19-CAR modified T cells with CAR delivered by lentivirus and Cas9 knockout of HPK1 | Xijing Hospital | China | NCT04037566 | 7/30/2019 | |
| plasmid delivery | ZFN | I | E7 oncogene of HPV16 and HPV18 deletion | HPV-related malignancy | In vivo | Vaginal suppository with polymer to facilitate delivery | Huazhong University of Science and Technology | China | NCT02800369 | 6/15/2016 |
| TALEN | I | E6 and E7 oncogene of HPV16 and HPV18 deletion | HPV-related malignancy | in vivo | plasmid in a gel containing a polymer to facilitate delivery | First Affiliated Hospital, Sun Yat-Sen University | China | NCT03057912 | 2/20/2017 | |
| TALEN | I | E6 and E7 oncogene of HPV16 and HPV18 deletion | HPV-related malignancy | In vivo | Plasmid in vaginal suppository with polymer to facilitate delivery | Huazhong University of Science and Technology | China | NCT03226470 | 7/21/2017 | |
| Cas9 | I | E6 and E7 oncogene of HPV16 and HPV18 deletion | HPV-related malignancy | In vivo | Plasmid in a gel containing a polymer to facilitate delivery | First Affiliated Hospital, Sun Yat-Sen University | China | NCT03057912 | 2/20/2017 | |
| Undefined, likely electroporation | Cas9 | I | Programmed cell death protein 1 (PD-1) knockout | Metastatic non-small cell lung cancer | Ex vivo | Modified T cells | Peking University | China | NCT02793856 | 6/8/2016 |
| Cas9 | I | Programmed cell death protein 1 (PD-1) knockout | Stage IV bladder cancer | Ex vivo | Modified T cells | Peking University | China | NCT02863913 | 8/11/2016 | |
| Cas9 | I | Programmed cell death protein 1 (PD-1) knockout | Metastatic renal cell carcinoma | Ex vivo | Modified T cells | Peking University | China | NCT02867332 | 8/15/2016 | |
| Cas9 | I | Programmed cell death protein 1 (PD-1) knockout | Hormone refractory prostate cancer | Ex vivo | Modified T cells | Peking University | China | NCT02867345 | 8/15/2016 | |
| Cas9 | I/II | Programmed cell death protein 1 (PD-1) knockout | EBV-positive, advanced stage malignancies | Ex vivo | Modified T cells selected for those targeting EBV positive cells | The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School | China | NCT03044743 | 2/7/2017 | |
| Cas9 | II | Programmed cell death protein 1 (PD-1) knockout | esophageal cancer | Ex vivo | Modified T cells | Hangzhou Cancer Center | China | NCT03081715 | 3/16/2017 | |
| Cas9 | n/a | CCR5 knockout | HIV | Ex vivo | Modified CD34+ hematopoietic stem cells | Affiliated Hospital to Academy of Military Medical Sciences | China | NCT03164135 | 5/23/2017 | |
| Cas9 | I/II | Cas9-mediated creation of CD19 and CD20 or CD19 and CD22 CAR-T cells | Leukemia | Ex vivo | CAR T cells to CD19 and CD20 or CD19 and CD22 | Chinese PLA General Hospital | China | NCT03398967 | 1/16/2018 | |
| Cas9 | I/II | Cytokine-induced SH2 protein (CISH) knockout | Metastatic gastrointestinal epithelial cancer | Ex vivo | Modified tumor-infiltrating lymphocytes | National Cancer Institute | U.S.A. | NCT03538613 | 5/28/2018 | |
| Cas9 | I | Programmed cell death protein 1 (PD-1) and TCR knockout | Mesothelin positive solid tumors | Ex vivo | CAR T cells to mesothelin with added PD-1 and TCR knockout | Chinese PLA General Hospital | China | NCT03545815 | 6/4/2018 | |
| Cas9 | I | CD7 knockout in CD7 CAR T cells | T-cell malignancies | Ex vivo | CAR T cells to CD7 and knockout of native CD7 to prevent self targeting | Baylor College of Medicine | U.S.A. | NCT03690011 | 10/1/2018 | |
| Cas9 | I | Correction of the hemoglobulin subunit β globulin gene | β-thalassemia | Ex vivo | Ex vivo modified hematopoietic stem cells | Allife Medical Science and Technology Co., Ltd. | Not specified | NCT03728322 | 11/2/2018 | |
| Cas9 | I | Programmed cell death protein 1 (PD-1) knockout | Mesothelin positive solid tumors | Ex vivo | CAR T cells to mesothelin with PD-1 knockout | Chinese PLA General Hospital | China | NCT03747965 | 11/20/2018 | |
| Cas9 | I/II | Cytokine-induced SH2 protein (CISH) knockout | Metastatic gastrointestinal epithelial cancer | Ex vivo | Modified tumor infiltrating lymphocytes | Masonic Cancer Center, University of Minnesota | U.S.A. | NCT04089891 | 9/13/2019 | |
| Long-term clinical follow-up post-intervention | ZFN | Follow-up | CCR5 knockout | HIV | Ex vivo | Modified CD4+ T cells, 12-year follow-up study | Sangamo Biosciences | U.S.A. | NCT04201782 | 12/17/2019 |
| TALEN | Follow-up | TCRα, TCRβ, CD52 knockout | Advanced lymphoid malignancy | Ex vivo | CD19-CAR modified T cells with CAR delivered by lentivirus and TALEN knockout CD52 and TCR to create universal T cells, 15-year follow-up study | Institut de Recherches Internationales Servier | U.K., Belgium, France, U.S.A. | NCT02735083 | 4/12/2016 | |
| Cas9 | Follow-up | Disruption of the erythroid enhancer to BCL11A gene | β-thalassemia and severe sickle cell anemia | Ex vivo | Ex vivo- modified hematopoietic stem cells, 15-year follow-up study | Vertex Pharmaceuticals Incorporated and CRISPR Therapeutics | U.S.A., U.K., Germany | NCT04208529 | 12/23/2019 |
U.S. clinical trials data base (clinicaltrials.gov) was accessed on 1/1/2020, trials not including interventions using gene editors were excluded. Abbreviations: CAR, chimeric antigen receptor; TCR, T-cell receptor.