Table 2.
Clinical CRISPR/Cas9 therapy in malignant, metabolic and inherited diseases
| Editor | Disease | Target gene | Editing outcome | Interventions | Therapeutic principle | References/identifier | Phase/status |
|---|---|---|---|---|---|---|---|
| CRISPR/Cas9 | Lymphoma | PD-1 / TCR | Targeted gene disruption and insertion | Engineered autologous anti-mesothelin CAR-T | Gene disruption and insertion | NCT03545815 | Phase 1 |
| NCT04637763 | Phase 1 | ||||||
| TRAC, β2M, and CD70 | Targeted gene disruption and insertion | Engineered allogeneic anti-cd70 CAR-T | Gene disruption and insertion | NCT04502446 | Phase 1 | ||
| HPK1 | Targeted gene disruption and insertion | Engineered autologous anti-CD19 CAR-T | Gene disruption and insertion | NCT04037566 | Phase 1 | ||
| Leukemia and lymphoma | B2M, CIITA and TRAC | Gene disruption and insertion | Engineered Allogeneic Anti-CD19 CAR-T | Gene disruption and insertion | NCT05037669 | Phase 1 | |
| Cancer | CISH | Targeted gene disruption | Engineered Tumor-Infiltrating Lymphocytes | Gene disruption | NCT04426669 | Phase 1/Phase 2 | |
| Myeloma | TRAC, TRBC and PD-1 | Targeted gene disruption and insertion | Engineered autologous anti-NY-ESO-1 TCR-T | Gene disruption and insertion | NCT03399448 | Phase 1 | |
| Multiple Myeloma | TRAC and B2M | Targeted gene disruption and insertion | Engineered Allogeneic Anti-BCMA CAR-T | Gene disruption and insertion | NCT04925206 | Phase 1 | |
| NCT03166878 | Phase 1/Phase 2 | ||||||
| Engineered Allogeneic Anti-cd19 CAR-T | Gene disruption and insertion | NCT04244656 | Phase 1 | ||||
| Renal Cell Carcinoma | TRAC and B2M | Targeted gene disruption and insertion | Engineered Allogeneic Anti-cd70 CAR-T | Gene disruption and insertion | NCT04438083 | Phase 1 | |
| B Acute Lymphoblastic Leukemia | CD52 and TRAC | Targeted gene disruption and insertion | Engineered Allogeneic Anti-cd19 CAR-T | Gene disruption and insertion | NCT04557436 | Phase 1 | |
| Solid Tumor | PD-1 | Targeted gene disruption | Infusions of CRISPR–Cas9 treated cytotoxic T lymphocytes (ex vivo) | Gene disruption | NCT03747965 | Phase 1 | |
| Gastric carcinoma, nasopharyngeal carcinoma, T cell lymphoma, adult Hodgkin lymphoma, diffuse large B cell lymphoma | PD-1 | Targeted gene disruption | Infusions of CRISPR–Cas9 treated cytotoxic T lymphocytes (ex vivo) | Gene disruption | NCT03044743 | Phase 1/Phase 2 | |
| Advanced Hepatocellular Carcinoma | PD-1 | Targeted gene disruption | Infusions of CRISPR–Cas9 treated cytotoxic T lymphocytes (ex vivo) | Gene disruption | NCT04417764 | Phase 1 | |
| Metastatic non-small cell lung cancer | PD-1 | Targeted gene disruption | Infusions of CRISPR–Cas9-treated T cells (ex vivo) | Gene disruption | NCT02793856 | Phase 1 | |
| Esophageal cancer | PD-1 | Targeted gene disruption | Infusions of CRISPR–Cas9-treated T cells (ex vivo) | Gene disruption | NCT03081715 | Not Applicable | |
| B Cell Leukemia | CD52 and TRAC | Targeted gene disruption and insertion | Engineered Allogeneic anti-CD19 and CD20 or CD22 CAR-T | Gene disruption and insertion | NCT03398967 | Phase 1/Phase 2 | |
| T cell malignancies | CD7 | Targeted gene disruption and insertion | Engineered Allogeneic anti-CD7 CAR-T | Gene disruption and insertion | NCT03690011 | Phase 1 | |
| B-cell Malignancy | TRAC and B2M | Targeted gene disruption and insertion | Infusions of CRISPR–Cas9 treated CD19-directed T cells (CTX110) (ex vivo) | Gene disruption and insertion | NCT04035434 | Phase 1 | |
| Sickle Cell Disease | β-globin | autologous hematopoietic stem progenitor cells | NCT04774536 | Phase 1/Phase 2 | |||
| β-Thalassemia | BCL11A enhancer | Targeted enhancer disruption | Engineered Autologous CD34 + Hematopoietic Stem and Progenitor Cells | Regualtion of gene expression | NCT03655678 | Phase 2/Phase 3 | |
| NCT04925206 | Phase 1 | ||||||
| NCT04208529 | Not Applicable | ||||||
| NCT03745287 | Phase 2/Phase 3 | ||||||
| NCT05477563 | Phase 3 | ||||||
| HBB | Mutation correction | Engineered Autologous Hematopoietic Stem and Progenitor Cells | Restore gene function | NCT03728322 | Early Phase 1 | ||
| Virus infection (HSV-1) | HSV-1 | DNA disruption | corneal injection of CRISPR/Cas9 mRNA targeting HSV-1 | Virus genome disruption | NCT04560790 | Not Applicable | |
| Virus infection (COVID-19) | PDCD1 and ACE2 | Targeted gene disruption | Engineered T lymphocytes | Gene disruption | NCT04990557 | Phase 1/Phase 2 | |
| HIV-1-infection | CCR5 | Targeted gene disruption | Engineered Allogeneic CD34 + Hematopoietic Stem and Progenitor Cells | Gene disruption | NCT03164135 | Not Applicable | |
| HPV-related Cervical Intraepithelial Neoplasia I | E6/E7 | Targeted gene disruption | Gel with Talen or Cas9 plasmids | Virus genome disruption | NCT03057912 | Phase 1 | |
| Leber congenital amaurosis type 10 (LCA 10) | CEP290 | Exon skipping | Subretinal injection of AGN-151587 (EDIT-101) (in vivo) | Gene correction | NCT03872479 | Phase 1/Phase 2 | |
| Base editor | heterozygous familial hypercholesterolemia (HeFH) / atherosclerotic cardiovascular disease (ASCVD) / uncontrolled hypercholesterolemia | pcsk9 | Targeted gene disruption | LNP-Base editor mRNA | Gene disruption | NCT05398029 | Phase 1 |
| β-thalassemia (TDT) /sickle cell disease (SCD) | BCL11a | Enhancer disruption | Base edited CD34 + hematopoietic stem | Regulation of gene expression | NCT05456880 | Phase 1/Phase 2 |