| β-thalassemia and sickle cell disease |
In human phase I trial |
BCL11A
|
Increased concentrations of fetal haemoglobin (HbF) |
(7, 8) |
| Sickle cell disease |
Ex vivo
|
β-globin gene |
Synthesis of wild-type haemoglobin |
(23) |
| Resistant CD19+ B cell acute lymphoblastic leukemia |
In human phase I trial |
Anti-CD19 chimeric antigen receptor |
Generation of universal T cell populations that target tumour cells, leading to negative flow cytometry |
(9) |
| Multiple refractory solid cancers including colorectal cancer, hormone-receptor-positive breast cancer, ovarian cancer, melanoma, and lung cancer |
In human phase I trial |
Mutational neoantigens-related genes |
Achievement of disease stability in about third of the subjects |
(10) |
| Orthotopic glioblastoma |
In vivo
|
PLK1
|
Reduction in primary and metastatic tumour growth and significant increase in mice survival |
(24) |
| Transthyretin amyloidosis |
In human phase I trial |
TTR
|
Significant drop in TTR protein |
(11) |
| Cystic fibrosis |
In vitro
|
CFTR
|
Increase in functional CFTR by more than 70% |
(25, 26) |
| Alpha-1 antitrypsin deficiency |
In vivo
|
SERPINA1
|
Decrease in the expressed mutation (Pi*ZZ) and its related phenotypic features |
(27-29) |
| Duchenne muscular dystrophy |
In vivo
|
DMD gene |
Restoration of functional dystrophin with subsequent improvement in muscular contractility |
(30-33) |
| HIV-1 infection |
In vivo
|
endogenous Igh locus in B cells |
Induction of sustainable humoral response |
(35) |
|
In vivo
|
Gag
|
Elimination of integrated proviral DNA and clearance of viremia |
(36) |
|
In vitro
|
tat and rev
|
Suppression of viral infection |
(37) |
|
In vitro
|
CCR5
|
Induction of indels in the CCR5 protein |
(38) |
| Tyrosinemia type 1 |
In utero of mice models |
HPD
|
Survival of Fah–/– mice and amelioration in liver function |
(40) |
| Autosomal dominant hypercholesterolemia |
In vivo
|
PCSK9
|
Decrease in LDL cholesterol concentrations |
(42-44) |
|
In vivo
|
LDLR
|
Restoration of wild-type LDLR, and decrease in atherogenic dyslipidemia as well as pathological features of atherosclerosis |
(45) |
|
In vitro
|
LDLR
|
Permanent repair of homozygous deletion in LDLR gene |
(46) |
| Leber congenital amaurosis type 10 |
In vitro and in vivo
|
CEP290
|
Correction of the disease-causing mutation |
(48, 49) |
|
In vitro
|
MAK
|
Restoration of the retinal transcript and protein in patient cells |
(50) |
| Retinitis pigmentosa |
In vivo
|
RPGR
|
Expression of full length RPGR ORF15 protein and disappearance of hallmark features of RPGR mutation |
(51) |
| Amyotrophic lateral sclerosis |
In vitro
|
SOD1 and FUS
|
Correction of SOD1 mutation in patient iPSCs |
(52) |
|
In vivo
|
SOD1
|
Increase in motoneurons, delay in disease onset, and prolongation in lifespan |
(53) |
|
In vitro and in vivo
|
C9ORF72
|
Reversal of major disease mechanisms |
(57) |
| Huntington’s disease |
In vivo
|
HTT
|
Decrease in neurotoxic inclusions, increase in survival and partial recovery in motor dysfunction |
(54) |
| Parkinson’s disease |
In vitro
|
LRRK2
|
Resuscitation of parkinsonism phenotypes in iPSC-derived dopaminergic neurons |
(55) |
|
In vitro and in vivo
|
SNCA
|
Reduction of α-synuclein overexpression, reactive microgliosis, dopaminergic neurodegeneration, and parkinsonian motor symptoms |
(58) |
| Alzheimer’s disease |
In vivo
|
App
|
Down-expression of amyloid precursor protein |
(59) |
|
In vitro
|
PSEN1
|
Partial restoration of amyloid-β 42/40 in human fibroblasts carrying PSEN1 mutation |
(56) |
| CRISPR-Cas9 - clustered regularly interspaced short palindromic repeats-associated protein 9. |
