|
| Target/mechanism of action | Construct | Results |
|
| Rev [30] | “Humanized” dominant-negative REV protein (huM10) and nontranslated marker gene (FX) as an internal control in retroviral vector | Gene marking in first months, then low or undetectable except in one patient when viral load increased. No serious adverse events. |
| RRE decoy [12, 33] | Retroviral-mediated transfer of an RRE decoy gene into bone marrow CD34+ cells | No adverse effects. 2 subjects’ cells detected containing both the RRE and LN vectors on the day after cell infusion. All subsequent samples negative for the L-RRE-neo vector. Cells containing the control LN vector detected up to 330 days. |
| Rev/tat ribozyme [34] | Tat and tat/rev ribozyme in autologous CD34+ cells and empty vector backbone in two patient groups with and without ablation | Trial 1: 3/5 patients showed low-frequency marking of PBMC with ribozyme and vector backbone. Trial 2: gene marked cells detected after infusion and to 1 year and RNA expression detected. |
| Tat/vpr ribozyme [4] | Phase I study: Moloney murine leukemia retroviral vector encoding a ribozyme versus control LNL6 vector in CD34+ HPSC | De novo production of myeloid and lymphoid cells. Degree of persistence of gene-containing cells dependent on transduced cell dose. |
| Tat/vpr ribozyme [32] | Phase II study: Moloney murine leukemia virus-based, replication-incompetent gamma retroviral vector with gene encoding a ribozyme vs placebo in CD34+ cells | No significant difference mean plasma viral load at primary endpoint but lower TWAUC and other indicators of biologic effect. No safety concerns. |
| Tat/rev, CCR5, TAR decoy [35] | Tat/rev short hairpin RNA, TAR decoy, and CCR5 ribozyme expressed from a self-inactivating lentiviral vector transduced in CD34+ cells, along with standard unmanipulated HPCs in 4 patients with HIV and non-Hodgkin’s lymphoma | Engraftment by 11 days. Low levels of gene marking observed up to 24 months. |
|
