Table 2.
Overview of the studies on PD models using CRISPR Cas9 and related editing strategies.
| PD model | Target gene | Target variation location | Delivery methods | Main results | References |
|---|---|---|---|---|---|
| iPSC and hESC | LRRK2 | p.G2019S | Transfection of helper-dependent adenoviral vectors | Pathological changes in the nucleus | Liu et al. (2012) |
| iPSC from PD patient | LRRK2 | p.Gly2019Ser | / | Delayed mitochondrial autophagy and impaired cellular respiration and metabolism | Hsieh et al. (2016) |
| iPSC from PD patient | PARK2 | Homozygous deletion of parkin exons 2–4 | / | Increased oxidative stress accompanied by activation of the Nrf2 pathway; Abnormal mitochondrial morphology and impaired mitochondrial turnover | Imaizumi et al. (2012) |
| iPSC from PD patient | PARK2 | Homozygous deletion of exons 6 and 7 | / | ||
| Human dopaminergic SH-SY5Y | UQCRC1 | p.Ala25Glyfs*27 | Electrotransfection of CRISPR Cas9 plasmid | Axonal degeneration and mitochondrial respiratory chain dysfunction in cells | Lin et al. (2020) |
| Drosophila | UQCRC1 | p.Tyr314Ser | Injection of CRISPR Cas9 system to Oregon R embryos | Age-dependent locomotor defects, dopaminergic neuronal loss, peripheral neuropathy, impaired respiratory chain complex III activity and aberrant mitochondrial ultrastructures in nigral neurons |
Lin et al. (2020) |
| Mouse | UQCRC1 | p.Tyr314Ser | Injection of CRISPR Cas9 system to one-cell stage embryos | ||
| Drosophila | tango14 | p. Gly217Ter | Injection of CRISPR Cas9 system to pre-blastoderm embryos | Shortened life span, cholesterol accumulation in dopaminergic neurons | Xue et al. (2022) |
| Zebrafish | DJ-1 | Frame shift from exon1 | Injection of CRISPR Cas9 system to one-cell stage embryos | Lower tyrosine hydroxylase levels, skeletal muscle respiratory failure, and lower body weight | Edson et al. (2019) |
| Zebrafish | GCH1 | p.T59Rfs27* | Injection of CRISPR Cas9 system to one-cell stage embryos | Monoamine neurotransmitter deficiency, motor deficit at 8dpf, death at 12dpf | Larbalestier et al. (2022) |
| Zebrafish | ATP12A2 | Frame shift from exon2 | Injection of CRISPR Cas9 system to one-cell stage embryos | Significant reduction in the number of TH+ neurons in the posterior nodes and locus ceruleus | Nyuzuki et al. (2020) |
| Mouse | VPS35 | p.D620N | Injection of CRISPR Cas9 system to pronuclei of one-cell embryos | Survival disadvantage, and DA release is significantly reduced in caudate-putamen | Ishizu et al. (2016) |
| Mouse | CDK5 | / | Stereotactic injection of the CRISPR Cas9 system into the dorsal striatum | Deficits in locomotor activity and disturbances in activity/rest behavior, and downregulation of dendritic length and decreased number of functional synapse in the brain | Zhou et al. (2022) |
| Mouse | PNPLA9 | p.R748W | Injection of CRISPR Cas9 system to one-cell stage embryos | Exercise disorders and accumulation of peroxisomal phospholipids | Sun et al. (2021) |
| Mouse | prkn/pink1/dj-1 | / | Editing ES cells by homing endonuclease technology combined with transfection and then transplanting ES into blastocysts | No obvious neuronal loss, normal behavior | Kitada et al. (2009) |
| Pig | SNCA | p.E46K, p.H50Q, p.G51D | Transfection of CRISPR Cas9 system into fbroblasts through Xfect and then performing SCNT | No obvious neuronal loss, normal behavior | Zhu et al. (2018) |
| Pig | PARK7 | / | Transfection of TALEN system into primary fetal fibroblast cells through electroporation and then performing SCNT | DJ-1 protein was repressed in all the detected tissues and all pigs die due to due to cloning defect | Yao et al. (2014) |
| Pig | PARK2 and PINK1 | First exon | Transfection of CRISPR Cas9 system into fbroblasts through electroporation and then performing SCNT | No obvious neuronal loss, normal behavior | Zhou et al. (2015) |
| Pig | Parkin/DJ-1/PINK1 | / | Injection of CRISPR Cas9 system to pronuclei of one-cell embryos | No obvious neuronal loss, normal behavior | Wang et al. (2016) |
| Monkey | PINK1 | / | / | Some died after birth, and surviving monkeys showed severe degeneration and death of neural cells in the brain | Yang et al. (2019b) |
| Monkey | PINK1 | Frame shift mutation | Injection of CRISPR Cas9 system to pronuclei of one-cell embryos | No obvious neuronal loss,normal behavior | Chen et al. (2021) |
| Monkey | PINK1 and DJ-1 | Second and third exons of PINK1, second and fourth second exons of DJ-1 | Stereotactic injection of AAV9-Packaged CRISPR Cas9 into specific brain regions | Severe loss of dopaminergic neurons and accumulation of pathology of a-synaptic nucleoprotein in the substantia nigra | Li et al. (2021) |