TABLE 1.
The gene editing therapeutic approaches for FSHD.
| Cas9/TALEN | Strategy | Target | Study | Method | Gene expression (residual) | Reference |
|---|---|---|---|---|---|---|
| dCas9 | KRAB | Prom/exon1 (DUX4) | In vitro | Lentivirus | 50% (TRIM43) | Himeda et al (2016) |
| dSaCas9 | SUV39H1 | Prom/exon1 (DUX4) | In vitro | Lentivirus | 50% (TRIM43) | Himeda et al (2021) |
| dSaCas9 | HP1gamma | Prom/exon1 (DUX4) | In vitro | Lentivirus | 50% (TRIM43) | Himeda et al (2021) |
| dSaCas9 | MeCP2 | Prom/exon1 (DUX4) | In vitro | Lentivirus | 45% (TRIM43) | Himeda et al (2021) |
| dSaCas9 | HP1α | Prom/exon1 (DUX4) | In vitro | Lentivirus | 35% (TRIM43) | Himeda et al (2021) |
| dSaCas9 | KRAB | Prom/exon1 (DUX4) | In vivo | AAV9 (IM) | 50% (Wfdc3) | Himeda et al (2021) |
| SpCas9 | HDR/KRAB | PAS (DUX4) | In vitro | Lentivirus | <20% (DUX4) | Das et al (2021) |
| SaCas9 | ABE | PAS (DUX4) | In vitro | Transfection | No ABE activity | Sikrova et al. (2021) |
| CJCas9 | ABE | PAS (DUX4) | In vitro | Transfection | No ABE activity | Sikrova et al (2021) |
| SpCas9 | ABE | PAS (DUX4) | In vitro | Transfection | 0% | Sikrova et al. (2021) |
| TALEN | HDR | PAS (DUX4) | in vitro | Transfection | 15% (TRIM43) | Joubert et al. (2020) |
| SpCas9 | DSB | PAS (DUX4) | In vitro | Transfection | Nd | Joubert et al. (2020) |
| NmCas9 | D5B | PAS (DUX4) | In vitro | Transfection | Nd | Joubert et al. (2020) |
| SpCas9 | DSB | SMCHD1 | In vitro | Transfection | 25% (DUX4) | Goossens et al (2019) |
KRAB, Krϋppel-associated box; Prom, promoter; ABE, adenine base editor; DSB, double-strand break. PAS, polyadenylation signal; AAV, adeno associated virus; IM, intramuscular injection
Nd, not done