Integration patterns and genotoxicity of gene transfer vector systems.
| Vector system . | Integration preferences . | Vector-related clonal events . |
|---|---|---|
| MLV retrovirus | Gene sequences, transcription start sites (TSS), expressed genes19,20 | T-cell leukemias in X-SCID clinical trial, rhesus macaque AML, murine hematopoietic tumors6,26,33 |
| HIV or SIV lentivirus | Gene sequences, expressed genes, transcription- associated histone modifications18,37,41 | Low rate compared with MLV in tumor-prone HSC mouse model34 |
| EIAV lentivirus | Gene sequences, actively expressed genes42 | Liver tumors after neonatal administration43 |
| Human foamy virus | No preference for genes or expressed genes. Preference for CpG island38 | None reported |
| Avian sarcoma Leukosis virus | Weak preference for active genes, no preference for TSS37 | None reported |
| ϕ31 phage integrase | Preference for mammalian pseudo-att sites40 | None reported |
| Sleeping beauty transposon | Weak preference for genes and TSS, preference for microsatellite regions44 | None reported |
| Zinc finger nucleases | Specific sequences targeted by zinc fingers39 | None reported |
| Adeno-associated virus | Integration hot spots, active genes, CpG islands, TSS45 | Liver tumors, controversial46,47 |
| Vector system . | Integration preferences . | Vector-related clonal events . |
|---|---|---|
| MLV retrovirus | Gene sequences, transcription start sites (TSS), expressed genes19,20 | T-cell leukemias in X-SCID clinical trial, rhesus macaque AML, murine hematopoietic tumors6,26,33 |
| HIV or SIV lentivirus | Gene sequences, expressed genes, transcription- associated histone modifications18,37,41 | Low rate compared with MLV in tumor-prone HSC mouse model34 |
| EIAV lentivirus | Gene sequences, actively expressed genes42 | Liver tumors after neonatal administration43 |
| Human foamy virus | No preference for genes or expressed genes. Preference for CpG island38 | None reported |
| Avian sarcoma Leukosis virus | Weak preference for active genes, no preference for TSS37 | None reported |
| ϕ31 phage integrase | Preference for mammalian pseudo-att sites40 | None reported |
| Sleeping beauty transposon | Weak preference for genes and TSS, preference for microsatellite regions44 | None reported |
| Zinc finger nucleases | Specific sequences targeted by zinc fingers39 | None reported |
| Adeno-associated virus | Integration hot spots, active genes, CpG islands, TSS45 | Liver tumors, controversial46,47 |