|
| Disease names | Related genes | Editing technologies | Model types | Clinical trials | Challenge points and limitation | Years |
|
Respiratory disorders | CF | CFTR | CRISPR | Organoids | \ | Proof of concept only, gene editing off-target effects; needs further evaluation for safety | 2013 [57] |
TALEN | Cells | \ | Delivery efficiency needs to be improved; targeting accuracy needs to be improved | 2019 [58] |
CRISPR | Patient-derived cells | \ | Difficulty of in vivo delivery, genetically corrected airway stem cell transplantation and recovery of in vivo mucus cilia transport | 2021 [59] |
NSCLC | PD-1 | CRISPR | \ | Phase I (first) | Underexpansion and low response rate of T cells after gene editing; small study sample | 2020 [60] |
Circulatory disorders | HC | Protein PCSK9 | MegNs | Macaques | \ | Off-target effects, with cytotoxicity, immunogenicity to be overcome | 2018 [61] |
NS-associated HCM | RAF1 | CRISPR | Patient-derived cells | \ | RAF1 lacks a nuclear localization sequence (NLS), its translocation mechanism is unknown, and the molecular mechanism of the disease needs to be further explored | 2019 [62] |
HC | Ldlr | CRISPR | Mouse | \ | Genome editing efficiency to be improved and off-target effects to be overcome | 2020 [63] |
NS-associated HCM | LZTR1 | CRISPR | Patient-derived cells | \ | Proof of concept only, needs in vivo evaluation, patient-specific iPSC-CM model is still immature and needs to be improved | 2020 [64] |
LDS | TGFBR1 | CRISPR | Patient-derived cells | \ | Needs further proof from in vivo experiments, off-target effects | 2021 [65] |
Infectious diseases | HIV | CCR5 | ZFN | \ | Yes | A serious adverse event was associated with the infusion of ZFN-modified autologous CD4 T cells, with off-target safety issues to be overcome | 2014 [66] |
ZFN | Mouse | \ | Reduced proliferation of editorial cells transplanted in vivo, delivery efficiency and targeting accuracy need to be improved | 2013 [67] |
TALEN | Cells | \ | Delivery efficiency and targeting accuracy need to be improved | 2015 [68] |
CRISPR | Mouse | \ | Safety issues to be further assessed | 2017 [69] |
CRISPR | \ | Yes | Off-target efficiency needs to be improved, targeting accuracy needs to be improved, and generalizability needs to be further assessed | 2019 [5] |
CRISPR | Patient-derived cells | \ | Off-target efficiency needs to be improved, and targeting accuracy needs to be improved | 2020 [70] |
Hematologic disorders | TDT & SCD | BCL11A | CRISPR | \ | Yes | No comprehensive genomic analysis of clinical samples and the generalizability of the results needs to be further determined | 2021 [71] |
TDT & SCD | HPFH5 | CRISPR | Cells | \ | Off-target effects to be overcome and safety to be improved | 2016 [72] |
SCD | HBB | CRISPR | Mouse | \ | The off-target efficiency needs to be reduced, and more sensitive off-target analysis methods are needed | 2019 [73] |
SCD | HBB | CRISPR | Humanized mouse | \ | Delivery methods to be optimized and delivery efficiency to be improved | 2021 [74] |
ALL | CD52 | TALEN | \ | Yes | Immunogenicity needs to be further reduced; safety needs to be further tested; small sample size | 2017 [75] |
MM | TRAC、CD52 | TALEN | Mouse | \ | Delivery efficiency needs to be improved, and long-term safety issues need to be further studied | 2019 [76] |
Neurological disorders | FXS | FMR1 | CRISPR | Mouse | \ | The off-target efficiency needs to be reduced, more sensitive off-target analysis methods are needed, and safety issues need to be further tested | 2018 [77] |
AD | TREM2 | CRISPR | Humanized SCD mouse | \ | Further analysis of the mechanism of action is needed to find effective therapeutic targets for disease treatment | 2020 [78] |
CD | ASPA | TALEN | Mouse | \ | Proof of concept only, how to achieve sustained efficacy remains to be addressed, and the issue of safety still needs to be improved | 2020 [79] |
Ophthalmology | XLRP | RP2 | CRISPR | Organoids | \ | Retinal-like organs are still immature and need further improvement | 2020 [80] |
LCA10 | CEP290 | CRISPR | Mouse | Yes | Impact of individual differences on safety of off-target effect delivery, durability of efficacy to be further assessed | 2019 [81] |
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