公开(公告)号：WO2016049163A2

公开(公告)日：2016-03-31

申请号：PCT/US2015051691

申请日：2015-09-23

申请人： BROAD INST INC ,  MASSACHUSETTS INST TECHNOLOGY

发明人： PLATT RANDALL JEFFREY ,  ZHANG FENG ,  SLAYMAKER IAN

IPC分类号： C12N15/10

CPC分类号： C12N15/63 ,  A01K67/0275 ,  A01K2217/072 ,  A01K2227/105 ,  A01K2267/0306 ,  A01K2267/0318 ,  C12N9/22 ,  C12N15/111 ,  C12N2310/10 ,  C12N2310/20 ,  C12N2320/11 ,  C12N2320/32 ,  C12N2330/51 ,  C12N2740/15041 ,  C12N2750/14341

摘要： The invention involves inducing a plurality e.g., 3-50 or more mutations (e.g., any whole number between 3 and 50 or more of mutations, with it noted that in some embodiments there can be up to 16 different RNA(s), e.g., sgRNAs each having its own a promoter, in a vector, such an AAV vector or a lentiviral vector and that when each sgRNA does not have its own promoter, there can be twice to thrice that amount of different RNA(s), e.g., sgRNAs, e.g., 32 or even 48 different guides delivered by one vector) in transgenic Cas9 eukaryotes to model a neuronal disease or disorder. The invention comprehends testing putative treatments with such models, e.g., testing putative chemical compounds that may be pharmaceutically relevant for treatment or gene therapy that may be relevant for treatment, or combinations thereof. The invention allows for the study of genetic diseases and putative treatments to better understand and alleviate a genetic disease or a condition, e.g., autism, autism-spectrum disease or disorder, obsessive compulsive disorder, or psychiatric disorders.

摘要翻译： 本发明涉及诱导多个例如3-50个或更多个突变（例如，3至50个或更多个突变之间的任何整数），其中注意到在一些实施方案中可以存在多达16个不同的RNA，例如， 在载体，如AAV载体或慢病毒载体中各自具有其自身启动子的sgRNA，并且当每个sgRNA不具有其自身启动子时，可存在两倍至三倍的不同RNA，例如sgRNA ，例如，由一个载体递送的32个或甚至48个不同的指导）转染到转基因Cas9真核生物中以模拟神经元疾病或病症。 本发明包括用这些模型测试假定的治疗，例如测试可能与治疗或可能与治疗相关的基因治疗在药学上相关的推定化学化合物或其组合。 本发明允许研究遗传疾病和推定的治疗以更好地理解和缓解遗传疾病或病症，例如孤独症，自闭症谱系疾病或障碍，强迫症或精神障碍。