CRISPR/Cas9 mediated somatic gene therapy for insertional mutations:the vibrator mouse model

作     者：Xin Fu Jie Zhu Yaou Duan Paul Lu Kang Zhang 

作者机构：Spine CenterXin Hua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China Guangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangzhou 510623China Department of NanoengineeringChemical Engineering Programand Moores Cancer CenterUniversity of California at San DiegoLa JollaCA 92093USA VA-San Diego Healthcare SystemSan DiegoCA 92161USA Department of NeurosciencesUniversity of California at San DiegoLa JollaCA 92093USA Center for Biomedicine and InnovationsFaculty of MedicineMacao University of Science and TechnologyMacaoChina 

出 版 物：《Precision Clinical Medicine》 (精准临床医学（英文）)

年 卷 期：2021年第4卷第3期

页      面：168-175页

学科分类：0710[理学-生物学] 1002[医学-临床医学] 07[理学] 08[工学] 09[农学] 071007[理学-遗传学] 0901[农学-作物学] 0836[工学-生物工程] 090102[农学-作物遗传育种] 

基　　金：This research was funded by the National Natural Science Foundation of China(grant No.3201101229) Macao Science and Technology Development Fund(grant No.015/2017/AFJ) Natural Science Foundation of Guangdong Province(grant No.2020A1515010072) 

主　　题：somatic gene editing neurodegenerative disease vibrator mouse model CRISPR/Cas9 Pitpna 

摘      要：Somatic gene therapy remains technically challenging,especially in the central nervous system(CNS).Efficiency of gene delivery,efficacy in recipient cells,and proportion of cells required for overall benefit are the key points needed to be considered in any therapeutic *** efforts have demonstrated the efficacy of RNA-guided nucleases such as CRISPR/Cas9 in correcting point mutations or removing dominant *** we used viral delivered Cas9 plasmid and two guide RNAs to remove a recessive insertional mutation,vibrator(vb),in the mouse *** vb mice expressed∼20%of normal levels of phosphatidylinositol transfer protein,α(PITPα)RNA and protein due to an endogenous retrovirus inserted in intron 4,resulting in early-onset tremor,degeneration of brainstem and spinal cord neurons,and juvenile *** in situ CRISPR/Cas9 viral treatment effectively delayed neurodegeneration,attenuated tremor,and bypassed juvenile *** studies demonstrate the potential of CRISPR/Cas9-mediated gene therapy for insertional mutations in the postnatal brain.