biostudies-literatureUnknown42(4)Chen ZZMutations of <i>PTEN-induced kinase I</i> (<i>PINK1</i>) cause early-onset Parkinson's disease (PD) with selective neurodegeneration in humans. However, current <i>PINK1</i> knockout mouse and pig models are unable to recapitulate the typical neurodegenerative phenotypes observed in PD patients. This suggests that generating <i>PINK1</i> disease models in non-human primates (NHPs) that are close to humans is essential to investigate the unique function of PINK1 in primate brains. Paired single guide RNA (sgRNA)/Cas9-D10A nickases and truncated sgRNA/Cas9, both of which can reduce off-target effects without compromising on-target editing, are two optimized strategies in the CRISPR/Cas9 system for establishing disease animal models. Here, we combined the two strategies and injected Cas9-D10AZoological research469-477https://www.ebi.ac.uk/biostudies/studies/S-EPMC8317192biostudies-literaturePMC8317192Zhi DLYan LNiu YYChen ZZYang QYLong CZShen BWang JYKang YGu XYfalseMutations of <i>PTEN-induced kinase I</i> (<i>PINK1</i>) cause early-onset Parkinson's disease (PD) with selective neurodegeneration in humans. However, current <i>PINK1</i> knockout mouse and pig models are unable to recapitulate the typical neurodegenerative phenotypes observed in PD patients. This suggests that generating <i>PINK1</i> disease models in non-human primates (NHPs) that are close to humans is essential to investigate the unique function of PINK1 in primate brains. Paired single guide RNA (sgRNA)/Cas9-D10A nickases and truncated sgRNA/Cas9, both of which can reduce off-target effects without compromising on-target editing, are two optimized strategies in the CRISPR/Cas9 system for establishing disease animal models. Here, we combined the two strategies and injected Cas9-D10A2021-01-01T00:00:00Z2021 Jul2025-04-19T20:42:17.115Z2022-02-11T01:06:26.53ZS-EPMC83171923421309310.24272/j.issn.2095-8137.2021.023