TY - JOUR T1 - Induction of core symptoms of autism spectrum disorders by in vivo CRISPR/Cas9-based gene editing in the brain of adolescent rhesus monkeys JF - bioRxiv DO - 10.1101/2020.08.03.233437 SP - 2020.08.03.233437 AU - Shi-Hao Wu AU - Xiao Li AU - Dong-Dong Qin AU - Lin-Heng Zhang AU - Tian-Lin Cheng AU - Zhi-Fang Chen AU - Bin-Bin Nie AU - Xiao-Feng Ren AU - Jing Wu AU - Wen-Chao Wang AU - Ying-Zhou Hu AU - Yilin Gu AU - Long-Bao Lv AU - Yong Yin AU - Xin-Tian Hu AU - Zi-Long Qiu Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/08/06/2020.08.03.233437.abstract N2 - Although CRISPR/Cas9-mediated gene editing is widely applied to mimic human disorders, whether acute manipulation of disease-causing genes in the brain leads to behavioral abnormalities in non-human primates remains to be determined. Here we induced genetic mutations in MECP2, a critical gene linked to Rett syndrome (RTT) and autism spectrum disorders (ASDs), in the hippocampus (DG and CA1–4) of adolescent rhesus monkeys (Macaca mulatta) in vivo via adeno-associated virus (AAV)-delivered Staphylococcus aureus Cas9 with sgRNAs targeting MECP2. In comparison to monkeys injected with AAV-SaCas9 alone (n = 4), numerous autistic-like behavioral abnormalities were identified in the AAV-SaCas9-sgMECP2-injected monkeys (n = 7), including social interaction deficits, abnormal sleep patterns, insensitivity to aversive stimuli, abnormal hand motions and defective social reward behaviors. Furthermore, some aspects of ASDs and RTT, such as stereotypic behaviors, did not appear in the MECP2 gene-edited monkeys, suggesting that different brain areas likely contribute to distinct ASD symptoms. This study showed that acute manipulation of disease-causing genes via in vivo gene editing directly led to behavioral changes in adolescent primates, paving the way for the rapid generation of genetically engineered non-human primate models for neurobiological studies and therapeutic development.Competing Interest StatementThe authors have declared no competing interest. ER -