Table 1.
A summary of anti HIV HSPC gene therapy research.
| Anti-HIV gene | Experimental Models | Salient results | References |
|---|---|---|---|
| CCR5 ribozyme | in-vitro | CCR5 reduction and HIV Inhibition in cell line | [21] |
| CCR5 ribozyme, anti-HIV shRNA, TAR decoy | clinical trial phase I/II – NCT01961063 | recruiting | City of Hope Medical Center |
| CCR5 ribozyme, anti-HIV shRNA, TAR decoy | clinical trial phase I/II | Transgene expression circulating cells | [87] |
| CCR5 ribozyme, anti-HIV shRNA, TAR decoy | in-vitro | HIV inhibition in cells line and PBMC | [24] |
| CCR5 ribozyme, anti-HIV shRNA, TAR decoy | in-vitro | HIV inhibition in human primay T cells | [22] |
| CCR5 ribozyme, anti-HIV shRNA, TAR decoy | humanized SCID mouse | HIV inhibition in cells from humanized mice | [86] |
| CCR5 shRNA | in-vitro | CCR5 knock down and HIV inhibition in human primary T cells | [26] |
| CCR5 shRNA | non-human primate | Stable CCR5 knock down in vivo, SIV inhibiton ex vivo | [28] |
| CCR5 shRNA | In-vitro | CCR5 and HIV-1 inhibition in macrophages derived from transduced HSPC | [29] |
| CCR5 shRNA | humanized BLT mouse | CCR5 knock down in lymphoid organs in vivo, HIV inhibitoin ex vivo | [30] |
| CCR5 shRNA/HIV LTRshRNA | humanized BLT mouse | CCR5 knock down and HIV resistance in T-cells | [32] |
| CCR5 shRNA | humanized BLT mouse | HIV resistance in memory T Cells | [31] |
| CCR5 miRNA | humanized NSG mouse | HIV resistance | [99] |
| CCR5 shRNA, C46 | in-vitro | no adverse effect on HSPC differentiation | [33] |
| CCR5 shRNA, C46 | humanized BLT mouse | Viral load reduction and HIV inhibition lymphoid tissue | [60] |
| CCR5 shRNA, C46 | clinical trial phase I/II – NCT01734850 | recruiting | Calimmune, Inc. |
| CCR5 ZFN | In-vitro humanized NOG mouse |
CCR5 kockout and HIV inhibition | [35] |
| CCR5 ZFN | humanized NSG mouse | CCR5 kockout and HIV inhibition | [36] |
| CCR5 ZFN | In-vitro | CCR5 kockout and HIV inhibition | [37] |
| CCR5 ZFN | In-vitro humanized NSG mouse |
CCR5 kockout and HIV inhibition | [39] |
| CCR5 ZFN | clinical trial phase I/II - NCT00842634 |
Safe autologous infusion of modified CD4+ cells | [118] |
| CCR5 ZFN | In-vitro humanized NSG mouse |
CCR5 knock out HSPC multilineage differentiation |
[106] |
| CCR5 ZFN | In-vitro humanized NSG mouse |
CCR5 knock out HIV inhibition |
[108] |
| CCR5 TALEN | In-vitro | CCR5 knock out in cell line | [41] |
| CCR5 TALEN | In-vitro | CCR5 knock out in cell line and primary cells | [40] |
| CCR5 TALEN | In-vitro | CCR5 knock out in iPSC | [48] |
| CCR5 CRISPR/Cas9 | In-vitro | CCR5 knock out in iPSC | [48] |
| CCR5 CRISPR/Cas9 | In-vitro humanized NSG mouse |
CCR5 knock out in HSPC Engraftement of modified HSPC |
[45] |
| CCR5 CRISPR/Cas9 | In-vitro | CCR5 knock out | [44] |
| CCR5 CRISPR/Cas9 | In-vitro | CCR5 knock out | [47] |
| CXCR4 shRNA | In-vitro | CXCR4 knock down and HIV Inhibition | [52] |
| CXCR4 ZFN | In-vitro humanized NSG mouse |
CXCR4 ZFN modified CD4+ T celll enrichment in humanized mice | [53] |
| CXCR4 CRISPR/Cas9 | In-vitro | HindIII restriction site knocked in CXCR4 gene in CD4+ primary cells | [54] |
| CXCR4 CRISPR/Cas9 | In-vitro | CXCR4 knockout and HIV-1 inhibition | [55] |
| CXCR4 ZFN; CCR5 ZFN | humanized NSG mouse | HIV inhibition | [89] |
| C46 | In-vitro | HIV inhibition | [58] |
| C46 | In-vitro | HIV, SIV, and SHIV inhibition | [59] |
| C46 | non-human primate | HIV/SHIV inhibition | [61] |
| C46 | clinical trial phase I/II | Transfert of autologous modified T cells | [62] |
| Human TRIMCyp | In-vitro and PBMC NSG mouse | HIV inhibition and viral load reduction | [65] |
| TRIM5α R322 | In-vitro | HIV inhibition | [67] |
| TRIM5α R332G-R335G | non-human primate | Survival advantage of gene modified cells | [68] |
| hu/maTRIM5α; CCR5 shRNA; TAR decoy | humanized BRG mouse | HIV inhibition | [88] |
| 2LTR-ZFProtein | In-vitro | HIV inhibition | [69] |
| Tre recombinase | In-vitro humanized RAG2 mouse |
Excision of the provirus DNA | [70,71] |
| HIV ZFN | In-vitro | Excision of the provirus from infected primary cells | [72] |
| HIV TALEN | In-vitro | Excision of the provirus from latently infected Jurkat cells | [74] |
| HIV CRISPR/Cas9 | In-vitro | Excision of the provirus from latently infected Jurkat cells | [73] |
| HIV CRISPR/Cas9 | Excision of the provirus and emergece of HIV resistance | [75] | |
| tat-vpr Ribozyme | clinical trial phase I/II | Lower HIV viral load | [117] |
| Tat siRNA | In-vitro | HIV inhibition in macrophages | [79] |
| TAR TALEN | In-vitro | Damage in up to 22% of the provirus integrated in the HeLa/LAV | [80] |
| Tat Nullbasic | In-vitro | HIV inhibition | [81] |
| RRE decoy | clinical trial phase I/II | low levels of gene-containing leukocytes 1 year after gene transfer | [119] |
| Gag-5 shRNA; Pol-1 shRNA; Pol-47shRNA; R/T-5 shRNA | In-vitro | 4shRNA combination prevents HIV escape mutations | [83] |
| CRIPER/Cas9 for latent HIV reactivation | In vitro | Latent HIV reactivation | [75–77] |
| Gag-5 shRNA; Pol-1 shRNA; Pol-47shRNA; R/T-5 shRNA | humanized BRG mouse | HIV inhibition | [84] |
| CD4ζCAR | In-vitro humanized BLT mouse |
HIV inhibition | [112] |
| CCR5Δ32/Δ32 bone marrow transplant | Boston patients | Relapse | [10] |
| CCR5Δ32/Δ32 bone marrow transplant | Berlin patient | An HIV cure | [5,6] |