| References | PD model | Target gene | Mains concequences | Risks of using CRISPR/Cas9 in gene therapy and Ethics |
| Hsieh et al. 2016 [54] | iPSC of a parkinsonian patient | LRRK2 | Delayed mitochondrial autophagy and impaired cellular respiration and metabolism. | Limitations of CRISPR-Cas9 systems include the efficacy of Cas9 delivery to cells or tissues, off-target effects and ethical concerns regarding the use of CRISPR technology in humans.
Adenoviral vectors (AdVs) are frequently used in clinical trials to deliver genes. AdVs can target both non-dividing and dividing cells.
Genome-editing techniques used in gene therapy can sometimes be imprecise and uncontrollable, leading to unexpected and unpredictable effects. These genetic errors, including “on-target” and “off-target” effects, can lead to unexpected results in genome editing.
CRISPR can also induce double-strand breaks (DSBs) in target DNA and, through genetic breaks, can trigger apoptosis rather than the intended genetic modification.
In the application of gene therapy using viral vectors, we must apply not only the ethical precautionary principle but also the fundamental bioethical principles of beneficence and non-maleficence. |
| Imaizumi et al., 2012 [55] | iPSC of a parkinsonian patient | PARC2 | Increased oxidative stress accompanied by activation of the Nrf2 pathway; Abnormal mitochondrial morphology and impaired mitochondrial turnover. | |
| Ishizu et al. 2016 [56] | Mice | VPS35 | Survival disadvantage and DA release is significantly reduced in the caudate putamen. | |
| Xu et al., 2023 [57] | Mice | CDK5 | Deficits in locomotor activity and disturbances in activity/rest behaviour, down-regulation of dendrite length and reduction in the number of functional synapses in the brain. | |
| Zhu et al. 2018 [58] | Pig | SNCA | No obvious neuronal loss, normal behavior. | |
| Yao et al., 2014 [59] | Pig | PARC7 | DJ-1 protein was repressed in all tissues detected and all pigs died due to a cloning defect. | |
| Wang et al. 2016 [60] | Pig | Parkin/DJ-1/ PINK1 | No obvious neuronal loss, normal behavior. | |
| Yang et al. 2019 [61] | Monkey | ROSE1 | Some died after birth and the surviving monkeys showed severe degeneration and death of neural brain cells. | |
| Li et al. 2021 [62] | Monkey | ROSE1 et DJ-1 | Severe loss of dopaminergic neurons and accumulation of synaptic nucleoprotein pathology in substantia nigra |