Table 3. Ongoing human clinical trials involving CRISPR/Cas9-based gene and cellular therapies.

Condition	Intervention	Phase	Type	Primary objective and study design	Principle	Start date	Finish date	ClinicalTrials. gov identifier
Metastatic non- small cell lung cancer	Biological: CRISPR/Cas9- mediated PD-1 knockout T cells from autologous origin Drug: cyclophosphamide, interleukin-2	Phase 1	Ex vivo	A dose-escalation study to evaluate the safety of ex vivo knocked-out, expanded, and selected PD-1 knockout engineered T cells that are infused back into the patient for the treatment of metastatic non- small cell lung cancer	Target cancer cell	August 2016	April 2018	NCT02793856
Muscle-invasive bladder cancer stage IV	Biological: CRISPR/Cas9- mediated PD-1 knockout T cells from autologous origin Drug: cyclophosphamide, interleukin-2	Phase 1	Ex vivo	A dose-escalation study of ex vivo knocked-out, expanded, and selected PD-1 knockout engineered T cells that are infused back into the patient for the treatment of muscle-invasive bladder cancer	Target cancer cell	September 2016	September 2019	NCT02863913
Hormone-refractory prostate cancer	Biological: CRISPR/Cas9- mediated PD-1 knockout T cells from autologous origin Drug: cyclophosphamide, interleukin-2	Phase 1	Ex vivo	A dose-escalation study of ex vivo knocked-out, expanded, and selected PD-1 knockout engineered T cells that are infused back into the patient for the treatment of castration- resistant prostate cancer	Target cancer cell	November 2016	December 2020	NCT02867345
Metastatic renal cell carcinoma	Biological: CRISPR/Cas9- mediated PD-1 knockout T cells from autologous origin Drug: cyclophosphamide, interleukin-2	Phase 1	Ex vivo	A dose-escalation study of ex vivo knocked-out, expanded, and selected PD-1 knockout engineered T cells that are infused back into the patient for the treatment of metastatic advanced renal cancer	Target cancer cell	November 2016	November 2020	NCT02867332
Advanced esophageal cancer	Biological: CRISPR/Cas9- mediated PD-1 knockout T cells from autologous origin Drug: cyclophosphamide, interleukin-2	Phase 2	Ex vivo	Evaluate the safety of ex vivo knocked-out, expanded, and selected PD-1 knockout T cells that are infused back into the patient for the treatment of advanced esophageal cancer	Target cancer cell	March 2017	December 2018	NCT03081715
Gastric carcinoma stage IV, nasopharyngeal carcinoma stage IV, T-cell lymphoma stage IV, adult Hodgkin lymphoma stage IV, diffuse large B-cell lymphoma stage IV	Biological: CRISPR/Cas9- mediated PD-1 knockout T cells from autologous origin Drug: fludarabine, cyclophosphamide, interleukin-2	Phase 1/2	Ex vivo	Evaluate the safety and clinical response of cell therapy using CRISPR-Cas9-mediated PD-1 knockout EBV-CTL cells for the treatment of advanced-stage EBV-associated malignancies	Target EBV- associated cancer cell	April 2017	March 2022	NCT03044743
HIV-1-infection	Biological: CRISPR/Cas9- mediated CCR5 modified CD34 + hematopoietic stem/ progenitor cells from donors Drug: anti-retroviral therapy	Phase 1	Ex vivo	Evaluate the safety and feasibility of allotransplantation with CRISPR/Cas9 CCR5 gene modified CD34 + hematopoietic stem/progenitor cells in HIV-infected patients with hematological malignances	Target CCR5- positive immune cell	May 2017	May 2021	NCT03164135
B-cell leukemia, B-cell lymphoma	Biological: gene-disrupted allogeneic CD19-directed BBζ CAR-T cells (termed UCART019) will be generated by combining the lentiviral delivery of CAR and CRISPR RNA electroporation to disrupt endogenous TCR and B2M genes	Phase 1/2	Ex vivo	Evaluate the feasibility, safety, and in vivo persistence of UCART019 adoptively transferred T cells in patients with relapsed or refractory CD19 + leukemia and lymphoma	Target cancer cell	June 2017	May 2022	NCT03166878
Human papillomavirus- related malignant neoplasm	Biological: TALEN and CRISPR/Cas9	Phase 1	In vivo	An open-label and triple-cohort study to evaluate the safety and efficacy of TALEN and CRISPR/ Cas9 plasmids for the treatment of HPV persistency and HPV- related cervical intraepithelial neoplasia	Disrupt HPV E6/E7 DNA	January 2018	January 2019	NCT03057912
Neurofibromatosis type 1	Biological: establish isogenic NF1 wild-type ( NF1 +/ +), NF1 heterozygous ( NF1 +/ −), and NF1 homozygous ( NF1 −/ −) patient-specific iPSC lines using CRISPR/Cas9 technology	Phase 1	Ex vivo	Establish an iPSC bank for disease phenotypic characterization, drug screening, and identification that can reverse or alleviate the disease phenotypes	Collection of stem cells	November 2017	June 2019	NCT03332030
Gastrointestinal infection	Biological: knockout CRISPR and gain-of-function CRISPR SAM Procedure: duodenal biopsy	Phase 1	Ex vivo	Identify and establish a list of host cellular proteins that mediate norovirus infection in a stem cell- derived human intestinal enteroid model	Genome- wide genetic screening	January 2018	December 2020	NCT03342547
Sickle cell disease	Overall genetic literacy, CRISPR-specific literacy, and general attitudes and beliefs toward CRISPR	Observational	Cross- sectional	Study the attitudes, beliefs, and opinions of those with SCD, parents of those with SCD, and providers on the use of CRISPR/ Cas9 gene-editing	–	October 2017	June 2018	NCT03167450

Based on ClinicalTrials.gov database on human clinical trials performed in the US and worldwide. B2M, beta-2-microglobulin; CAR, chimeric antigen receptor; CCR5, C-C chemokine receptor type 5; CTL, cytotoxic T-lymphocyte; EBV, Epstein-Barr virus; HPV, human papillomavirus; iPSC, induced pluripotent stem cell; NF1, neurofibromatosis type 1; PD-1, programmed cell death protein 1 gene; SCD, sickle cell disease; TALEN, transcription activator-like effector nuclease; TCR, T-cell receptor.