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Table 1 Characteristics of TGA-mediating methods

From: An update on targeted gene repair in mammalian cells: methods and mechanisms

Method: ssODNs SDF TFO AAV ZFN
Repair pathways involved NER, HDR? (MMR and NHEJ are suppressive) SFHR NER, NHEJ? MMR? HDR? HDR, NHEJ HDR, NHEJ
Correction efficiency a 0.1-5% (somatic cells) ~0.1% (ESCs) 0.2-20% (somatic cells) 0.025% (ESCs) 0.1-1.5% (somatic cells) 9.86%-65% (somatic cells) ~1% (ESCs and iPSCs) ~18-30% (somatic cells) 0.15-5% (iPSCs + ESCs)
Advantages No integration of exogenous DNA, synthesis, stable, reproducible results Reproducible results, potent episomal repair, artifacts can be circumvented Synthesis, low toxicity, target specific, functional in hHPCs, stable target-complex formation High efficiency and fidelity, effective in vivo delivery, broad cell type target field, low pathogenicity High efficiency, known repair mechanism, normal cell cycle profiles, low background integrations, target silent genes
Disadvantages Unknown repair mechanism, limited sequence size, PCR artifacts, genotoxicity, cell replication dependency SFHR mechanism unknown, depend on HDR-like mechanism, synthesis (PCR) Unknown repair mechanism, homopurine target restriction, G-C-rich sequences, weak DNA-binding, cellular death Safety concerns, size limitation, integration of exogenous DNA, random integrations, cellular death Synthesis, off-target cleavage, integration of exogenous DNA, multiple transductions
Targeted disease genes Dystrophin
α-D-glucosidase
β-PDE
TYR
CFTR
DNA-PKcs
Dystrophin
β-globin
SMN1
β-globin COL1A1
COL1A2
FANCA
Fah
CFTR
CCR5
IL2Rγ
CFTR
HoxB13
TYR
References b [4, 9, 12, 14, 41, 4649, 51, 52, 54, 62, 116, 117] [4, 8, 35, 39, 40, 63, 64, 118121] [16, 6669, 80, 84, 122] [4, 11, 31, 54, 85, 88, 90, 92, 93, 123, 124] [6, 10, 12, 13, 102, 104, 114, 125127]
  1. a) Note that the correction efficiencies might not be directly comparable due to differences in determination (e.g. efficiency vs. efficacy, factoring in targeting frequency, in vivo vs. in vitro conditions, etc.).
  2. b) References used to construct table.