Comparison of LV-mediated gene addition and genome-editing strategies for treating β-hemoglobinopathies
| . | LV-mediated gene addition strategies . | HDR-based genome-editing strategies . | NHEJ-based genome-editing strategies . |
|---|---|---|---|
| Therapeutic gene expression | Low/intermediate (depending on the VCN) | High | High |
| Efficiency in human HSCs | High | Low/intermediate | High |
| Safety | High/intermediate | Potentially high | Potentially high |
| Genotoxic risks | Oncogene transactivation, generation of aberrant transcripts, gene inactivation | Off-targets, large genomic rearrangements, β-globin gene knockout (SCD) | Off-targets, large genomic rearrangements |
| Costs | High (viral delivery) | High (viral delivery)/low (nonviral delivery) | Low (nonviral delivery) |
| . | LV-mediated gene addition strategies . | HDR-based genome-editing strategies . | NHEJ-based genome-editing strategies . |
|---|---|---|---|
| Therapeutic gene expression | Low/intermediate (depending on the VCN) | High | High |
| Efficiency in human HSCs | High | Low/intermediate | High |
| Safety | High/intermediate | Potentially high | Potentially high |
| Genotoxic risks | Oncogene transactivation, generation of aberrant transcripts, gene inactivation | Off-targets, large genomic rearrangements, β-globin gene knockout (SCD) | Off-targets, large genomic rearrangements |
| Costs | High (viral delivery) | High (viral delivery)/low (nonviral delivery) | Low (nonviral delivery) |