Table 1 Anti-HIV-1 gene therapy landscape
Therapeutic approach | Gene therapy | Interventions | Targets | Identifier | Stage/status | Company/Institute |
|---|---|---|---|---|---|---|
Drug shRNA peptide | Dual anti-HIV gene Transfer construct, LVsh5/C46 (Cal) | CCR5 shRNA; C46 peptide Busulfan | Host co-receptor; viral Env; transplant conditioning | NCT01734850 | Phase I/II recruiting | Calimmune/CalTech/UCLA |
shRNA | Long term follow up of delayed adverse events in Cal-1 recipients | Blood test for general health, complete blood count and Cal-1 specific analyses | NCT02390297 | Recruiting by invitation | Calimmune/CalTech/UCLA | |
Endoribonuclease | Redirected MazF-CD4 autologous T-cells | CCR5 MazF | Host co-receptor | NCT01787994 | Phase I ongoing | University of Pennsylvania |
Ribozyme | Autologous CD34+ HSCs transduced with anti-HIV-1 ribozyme (OZ1) | Tat-vpr anti-HIV ribozyme | tat-vpr mRNA | NCT00074997 | Phase II completed | Janssen-Cilag Pty Ltd, UCLA |
Ribozyme | Long term follow up of OZ1 Gene therapy | Blood test for quantitative marking of the gene transfer product in PBMCs overtime | NCT01177059 | Phase II Recruiting by invitation | Janssen-Cilag Pty Ltd, UCLA | |
Antisense | Tolerability and therapeutic effects of repeated doses of autologous T cells with VRX496 | VRX496 antisense RNA | Env mRNA | NCT00295477 | Phase I/II Ongoing/ not recruiting | University of Pennslyvernia/NIAID |
Antisense | Safety and efficacy of T-cell genetic immunotherapy | VRX496 antisense RNA | Env mRNA | NCT00131560 | Phase II Ongoing | VIRxSYS Corporation |
Ribozyme | L-TR/Tat-neo in HIV+ Patients with Non-Hodgkin’s Lymphoma | Tat ribozyme | Tat-rev mRNA | NCT00002221 | Phase II completed | Ribozyome/City of Hope |
Inhibitory peptides | M87o autologous HSCs for HIV+ patients with malignant disease | C46 peptide | Viral Env | NCT00858793 | Phase I/II suspended | University Medical Center Hamburg-Eppendorf |
Ribozyme, inhibitory peptide | C46/CCR5/P140K modified autologous HSCs in patients with lymphoma | C46 peptide, CCR5 ribozyme, MGMTP140Â K mutant | Viral Env, CCR5 mRNA, Alkylating agent resistance | NCT02343666 | Phase I, recruiting | Fred Hutchinson Cancer Research Center/NCI/NHLBI |
shRNA,peptide | Autologous transplantation of HSCs with LVsh5/C46 (Cal-1) for treatment of HIV-related lymphoma | CCR5 shRNA, C46 peptide | Host co-receptor, viral Env | NCT02378922 | Phase I recruiting | Fred Hutchinson Cancer Research Center/NCI |
shRNA, ribozyme,RNA decoy, drugs | rHIV7-shI-TAR-CCR5RZ-transduced HSC in patient with AIDS-related Non-Hodgkin Lymphoma | tat/rev shRNA, TAR decoy, CCR5 ribozyme, Prednisone, Rituximab, Etoposide, Doxorubicin Hydrochloride, Vincristine Sulfate, Cyclophosphamide | Viral mRNA, Viral tat proteinm, CCR5 mRNA, Transplant conditioning | NCT02337985 | Pilot recruiting | City of Hope Medical Center/NCI |
shRNA, ribozyme,RNA decoy, drugs | rHIV7-shI-TAR-CCR5RZ-transduced HSC in patient with AIDS-related Non-Hodgkin Lymphoma | tat/rev shRNA, TAR decoy, CCR5 ribozyme, Busulfan | Viral mRNA, Viral tat proteinm, CCR5 mRNA | NCT01961063 | Pilot recruiting | City of Hope Medical Center/NCI |
shRNA, ribozyme,RNA decoy, drugs | rHIV7-shI-TAR-CCR5RZ-transduced HSC in patient undergoing stem cell transplant for AIDS-related lymphoma | tat/rev shRNA, TAR decoy, CCR5 ribozyme, carmustine, cyclophosphamide, etoposide | viral mRNA, viral tat protein, CCR5 mRNA, transplant conditioning | NCT00569985 | Pilot ongoing, not recruiting | City of Hope Medical Center/NCI |
shRNA, RNA decoy | shRNA/TRIM5alpha/TAR decoy-transduced Autologous HSC in patient with HIV-Related Lymphoma | CCR5 shRNA, RNF88,TAR decoy | Host co-receptor, Gag p24, Viral tat protein | NCT02797470 | Phase I/II | City of Hope Medical Center/NCI |
RNA decoy | RNA decoy (ex vivo retroviral modified CD34+ HPC) | Rev reponse element decoy | Rev Protein | NCT00001535 | Phase 0-pilot | Children’s Hospital |
Redirected high affinity gag-specific autologous T cells | WT-gag-TCR or alpha/6-gag-TCR | CD8 TCR | NCT00991224 | Phase I completed | University of Pennslyvernia/Adaptimmune | |
ZFN | T-cells modified at CCR5 gene by ZFN SB-728mR | CCR5 ZFN | CCR5 DNA | NCT02388594 | Phase 1 recruiting | University of Pennsylvania/NIAID |
Repeated doses of SB-728mR-T after cyclophosphamide conditioning in HIV+ on HAART | CCR5 ZFN (SB-728mR-T) | CCR5 DNA | NCT02225665 | PHASE I/II ongoing | Sangamo biosciences | |
Autologous T cells modified at CCR5 gene by ZFN SB-728 | CCR5 ZFN | CCR5 DNA | NCT00842634 | Phase 1 completed | Sangamo biosciences/ Uni. Of Pennsylvania | |
Autologous T-cells genetically modified at the CCR5 gene by zinc finger nucleases (SB-728-T) in HIV-infected patients | CCR5 ZFN | CCR5 DNA | NCT01044654 | Phase I completed | Sangamo Therapeutics | |
Safety of ZFN CCR5-modified HPS/progenitor cells in HIV+ | SB-728mR-HSPC infusion after busulfan conditioning | CCR5 DNA | NCT02500849 | Phase 1 | City of Hope Medical Center|Sangamo Therapeutics | |
Autologous T-cells genetically modified at the CCR5 Gene by zinc finger nucleases in HIV-infected subjects | CCR5 ZFN (SB-728-T) | CCR5 DNA | NCT01252641 | Phase I/II completed | Sangamo Therapeutics | |