典型文献
Long-term correction of hemophilia B through CRISPR/Cas9 induced homology-independent targeted integration
文献摘要：
CRISPR/Cas9-mediated site-specific insertion of exogenous genes holds potential for clinical applications.However,it is still infeasible because homologous recombination(HR)is inefficient,especially for non-dividing cells.To overcome the challenge,we report that a homology-independent targeted integration(HITI)strategy is used for permanent integration of high-specificity-activity Factor Ⅸ variant(F9 Padua,R338L)at the albumin(Alb)locus in a novel hemophilia B(HB)rat model.The knock-in efficiency reaches 3.66％,as determined by droplet digital PCR(ddPCR).The clotting time is reduced to a normal level four weeks after treatment,and the circulating factor Ⅸ(FⅨ)level is gradually increased up to 52％of the normal level over nine months even after partial hepatectomy,demonstrating the amelioration of hemophilia.Through primer-extension-mediated sequencing(PEM-seq),no significant off-target effect is detected.This study not only provides a novel model for HB but also identifies a promising therapeutic approach for rare inherited diseases.
文献关键词：
中图分类号：
作者姓名：
Xi Chen;Xuran Niu;Yang Liu;Rui Zheng;Lei Yang;Jian Lu;Shuming Yin;Yu Wei;Jiahao Pan;Ahmed Sayed;Xueyun Ma;Meizhen Liu;Fengxiang Jing;Mingyao Liu;Jiazhi Hu;Liren Wang;Dali Li
作者机构：
Shanghai Frontiers Science Center of Genome Editing and Cell Therapy,Shanghai Key Laboratory of Regulatory Biology,Institute of Biomedical Sciences and School of Life Sciences,East China Normal University,Shanghai 200241,China;The MOE Key Laboratory of Cell Proliferation and Differentiation,Genome Editing Research Center,School of Life Sciences,Peking-Tsinghua Center for Life Sciences,Peking University,Beijing 100871,China;Xinhua Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200092,China;Biochemistry Laboratory,Chemistry Department,Faculty of Science,Assiut University,Assiut 71516,Egypt;Shanghai Turtle Technology Co.,Shanghai 201900,China
文献出处：
引用格式：
[1]Xi Chen;Xuran Niu;Yang Liu;Rui Zheng;Lei Yang;Jian Lu;Shuming Yin;Yu Wei;Jiahao Pan;Ahmed Sayed;Xueyun Ma;Meizhen Liu;Fengxiang Jing;Mingyao Liu;Jiazhi Hu;Liren Wang;Dali Li-.Long-term correction of hemophilia B through CRISPR/Cas9 induced homology-independent targeted integration)[J].遗传学报,2022(12):1114-1126
A类：
HITI,R338L
B类：
Long,correction,hemophilia,through,CRISPR,Cas9,induced,homology,independent,targeted,integration,mediated,site,insertion,exogenous,genes,holds,potential,clinical,applications,However,still,infeasible,because,homologous,recombination,inefficient,especially,dividing,cells,To,overcome,challenge,report,that,strategy,used,permanent,high,specificity,activity,Factor,variant,F9,Padua,albumin,Alb,locus,novel,HB,model,knock,efficiency,reaches,determined,by,droplet,digital,ddPCR,clotting,reduced,normal,level,four,weeks,after,treatment,circulating,gradually,increased,up,nine,months,even,partial,hepatectomy,demonstrating,amelioration,Through,primer,extension,sequencing,PEM,significant,off,effect,detected,This,study,not,only,provides,but,also,identifies,promising,therapeutic,approach,rare,inherited,diseases
AB值：
0.683998
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机标中图分类号，由域田数据科技根据网络公开资料自动分析生成，仅供学习研究参考。
