公开(公告)号：US11896679B2

公开(公告)日：2024-02-13

申请号：US16851636

申请日：2020-04-17

申请人： The Johns Hopkins University

发明人： Vinod Jaskula-Ranga ,  Donald Zack

IPC分类号： A61K48/00 ,  C12N15/85 ,  C12N15/113 ,  C12N15/63 ,  C12N15/90 ,  C12N15/11 ,  C12N15/861 ,  C12N15/86 ,  C12Q1/68

CPC分类号： A61K48/0066 ,  C12N15/111 ,  C12N15/1138 ,  C12N15/63 ,  C12N15/85 ,  C12N15/86 ,  C12N15/8616 ,  C12N15/907 ,  C07K2319/10 ,  C07K2319/60 ,  C12N2310/10 ,  C12N2310/20 ,  C12N2330/51 ,  C12N2750/14133 ,  C12N2750/14143 ,  C12N2830/205 ,  C12N2830/85

摘要： The presently disclosed subject matter provides compositions and methods for the expression of CRISPR guide RNAs using the H1 promoter. In particular, compositions and methods are provided for the use of the H1 promoter to express CRISPR guide RNA (gRNA) with altered specificity of the 5′ nucleotide, as well as use of the H1 promoter sequence as a bidirectional promoter to express Cas9 nuclease and the gRNA simultaneously. Compositions and methods are also provided for the expression and regulation of gRNA expression in vivo through the use of RNA ribozymes and regulatable aptazymes.

公开(公告)号：US20180104289A1

公开(公告)日：2018-04-19

申请号：US15565065

申请日：2016-04-07

申请人： The United States of America, as represented by The Secretary, of Health And Human Services

发明人： Charles P. Venditti ,  Randy Chandler ,  William J. Pavan

IPC分类号： A61K35/761 ,  A61K48/00 ,  C07K14/075 ,  C12N7/04 ,  C12N15/861 ,  A61P25/28 ,  A61P3/00

CPC分类号： A61K35/761 ,  A61K48/005 ,  A61P3/00 ,  A61P25/28 ,  C07K14/075 ,  C12N7/04 ,  C12N15/86 ,  C12N15/8616 ,  C12N2710/10022 ,  C12N2710/10034 ,  C12N2710/10045 ,  C12N2750/14143

摘要： Provided herein are compositions and methods for the viral gene therapy (e.g., AAV-directed gene therapy) of cholesterol storage diseases or disorders, such as Niemann-Pick disease, Type C.

公开(公告)号：US11859179B2

公开(公告)日：2024-01-02

申请号：US16611581

申请日：2018-05-09

申请人： University of Massachusetts

发明人： Christian Mueller ,  Abbas Abdallah

IPC分类号： C12N15/861 ,  C12N15/11 ,  A61K35/76 ,  C12N9/22 ,  C12N15/86 ,  C12N15/90

CPC分类号： C12N15/11 ,  A61K35/76 ,  C12N9/22 ,  C12N15/86 ,  C12N15/8616 ,  C12N15/907 ,  C12N2310/20 ,  C12N2750/14143 ,  C12N2750/14171 ,  C12N2800/80

摘要： Aspects of the disclosure relate to recombinant gene editing complexes comprising a recombinant gene editing protein and guide RNA (gRNA) that specifically hybridizes to a region of a C90RF72 gene (e.g., a region flanking a G4C2 repeat or within a exonic region of the gene).

公开(公告)号：US20180327778A1

公开(公告)日：2018-11-15

申请号：US15975500

申请日：2018-05-09

申请人： The Regents of the University of California

发明人： Xianjin Zhou

IPC分类号： C12N15/85 ,  C12N15/861 ,  A01K67/027

CPC分类号： C12N15/8509 ,  A01K67/0276 ,  A01K2267/0312 ,  A61P25/28 ,  C12N5/0619 ,  C12N15/8616 ,  C12N2310/122

摘要： Provided are methods of making and using animal models for brain inflammation and white matter degeneration.

公开(公告)号：US09968689B2

公开(公告)日：2018-05-15

申请号：US15236152

申请日：2016-08-12

申请人： Wayne State University

发明人： Zhuo-Hua Pan

IPC分类号： A61K48/00 ,  C07K14/47 ,  C07K14/705 ,  C12N15/861 ,  A61K38/00

CPC分类号： A61K48/005 ,  A61K38/00 ,  C07K14/4702 ,  C07K14/705 ,  C07K2319/01 ,  C12N15/8616 ,  C12N2750/14143

摘要： Microbial type rhodopsins, such as the light-gated cation-selective membrane channel, channelrhodopsin-2 (Chop2/ChR2) or the ion pump halorhodopsin (HaloR) are expressed in retinal ganglion cells upon transduction using recombinant AAV vectors. Selective targeting of these transgenes for expression in discrete subcellular regions or sites is achieved by including a sorting motif in the vector that can target either the central area or surround (off-center) area of these cells. Nucleic acid molecules comprising nucleotide sequences encoding such rhodopsins and sorting motifs and their use in methods of differential expression of the transgene are disclosed. These compositions and methods provide significant improvements for restoring visual perception and various aspects of vision, particular in patients with retinal disease.

公开(公告)号：US11850289B2

公开(公告)日：2023-12-26

申请号：US16851636

申请日：2020-04-17

申请人： The Johns Hopkins University

发明人： Vinod Jaskula-Ranga ,  Donald Zack

IPC分类号： A61K48/00 ,  C12N15/85 ,  C12N15/113 ,  C12N15/63 ,  C12N15/90 ,  C12N15/11 ,  C12N15/861 ,  C12N15/86 ,  C12Q1/68

CPC分类号： A61K48/0066 ,  C12N15/111 ,  C12N15/1138 ,  C12N15/63 ,  C12N15/85 ,  C12N15/86 ,  C12N15/8616 ,  C12N15/907 ,  C07K2319/10 ,  C07K2319/60 ,  C12N2310/10 ,  C12N2310/20 ,  C12N2330/51 ,  C12N2750/14133 ,  C12N2750/14143 ,  C12N2830/205 ,  C12N2830/85

摘要： The presently disclosed subject matter provides compositions and methods for the expression of CRISPR guide RNAs using the H1 promoter. In particular, compositions and methods are provided for the use of the H1 promoter to express CRISPR guide RNA (gRNA) with altered specificity of the 5′ nucleotide, as well as use of the H1 promoter sequence as a bidirectional promoter to express Cas9 nuclease and the gRNA simultaneously. Compositions and methods are also provided for the expression and regulation of gRNA expression in vivo through the use of RNA ribozymes and regulatable aptazymes.

公开(公告)号：US11773409B2

公开(公告)日：2023-10-03

申请号：US16607029

申请日：2018-04-23

申请人： The Board of Trustees of the Leland Stanford Junior University

发明人： Rasmus O. Bak ,  Matthew Porteus ,  Sriram Vaidyanathan

IPC分类号： C12N15/00 ,  C12N15/90 ,  C12N9/22 ,  C12N15/86 ,  C12N15/861 ,  A61K35/76 ,  A61K39/235 ,  A61K48/00 ,  C07K14/075

CPC分类号： C12N15/902 ,  A61K35/76 ,  C12N9/22 ,  C12N15/86 ,  C12N15/8616 ,  A61K39/235 ,  A61K48/005 ,  C07K14/075 ,  C12N15/907 ,  C12N2310/20 ,  C12N2310/313 ,  C12N2710/10043 ,  C12N2750/14141 ,  C12N2800/40

摘要： The present invention relates to a system and method for efficiently modifying the genome of cells to treat diseases via sequential homologous recombination using CRISPR/Cas-mediated genome editing with donor DNA delivered by two or more adeno-associated virus (AAV) vectors.

公开(公告)号：US20160333377A1

公开(公告)日：2016-11-17

申请号：US15152960

申请日：2016-05-12

申请人： Seattle Children's Hospital (dba Seattle Children's Research Institute)

发明人： Andrew Scharenberg ,  David Rawlings ,  Michael C. Jensen ,  Kamila Gwiazda ,  Alexandra Grier

IPC分类号： C12N15/90 ,  C12N7/00 ,  A61K38/46 ,  C12N15/86

CPC分类号： C12N15/907 ,  A61K38/465 ,  A61K48/005 ,  A61P35/00 ,  C12N7/045 ,  C12N15/113 ,  C12N15/86 ,  C12N15/8616 ,  C12N2310/20 ,  C12N2750/14143 ,  C12N2800/80

摘要： Disclosed herein are nuclease-based systems for genome editing and methods of using the system for genome editing. Also, disclosed are approaches to enhance Cas9-mediated gene editing efficiency in primary human cells with minimal toxicity when using adeno-associated virus vectors (AAV) to express the guide RNAs necessary for CRISPR/Cas9-based genome editing in the presence of helper proteins.

摘要翻译： 本文公开了用于基因组编辑的基于核酸酶的系统和使用该系统进行基因组编辑的方法。 此外，还公开了当使用腺相关病毒载体（AAV）在辅助蛋白存在下表达基于CRISPR / Cas9的基因组编辑所需的指导RNA时，以最小的毒性增强原代人细胞中Cas9介导的基因编辑效率的方法 。

公开(公告)号：US09453241B2

公开(公告)日：2016-09-27

申请号：US13696252

申请日：2011-05-04

申请人： Zhuo-Hua Pan

发明人： Zhuo-Hua Pan

IPC分类号： C12N15/861 ,  C07K14/705 ,  A61K48/00 ,  C12N15/85 ,  C07K14/47

CPC分类号： A61K48/005 ,  A61K38/00 ,  C07K14/4702 ,  C07K14/705 ,  C07K2319/01 ,  C12N15/8616 ,  C12N2750/14143

摘要： Microbial type rhodopsins, such as the light-gated cation-selective membrane channel, channel-rhodopsin-2 (Chop2/ChR2) or the ion pump halorhodopsin (HaloR) are expressed in retinal ganglion cells upon transduction using recombinant AAV vectors. Selective targeting of these transgenes for expression in discrete subcellular regions or sites is achieved by including a sorting motif in the vector that can target either the central area or surround (off-center) area of these cells. Nucleic acid molecules comprising nucleotide sequences encoding such rhodopsins and sorting motifs and their use in methods of differential expression of the transgene are disclosed. These compositions and methods provide significant improvements for restoring visual perception and various aspects of vision, particular in patients with retinal disease.

摘要翻译： 在重组AAV载体转导后，在视网膜神经节细胞中表达微生物型视紫质，例如光门控阳离子选择性膜通道，通道 - 视紫红质-2（Chop2 / ChR2）或离子泵卤素视紫红质（HaloR）。 通过在可以靶向这些细胞的中心区域或环绕（偏心）区域的载体中包含排序基序来实现用于在离散亚细胞区域或位点中表达的这些转基因的选择性靶向。 公开了包含编码这种视紫红质和排序基序的核苷酸序列的核酸分子及其在转基因的差异表达方法中的用途。 这些组合物和方法为恢复视觉感知和视力各方面提供了显着的改进，特别是视网膜疾病患者。

公开(公告)号：US20240167025A1

公开(公告)日：2024-05-23

申请号：US18505163

申请日：2023-11-09

申请人： University of Massachusetts

发明人： Christian Mueller ,  Abbas Abdallah

IPC分类号： C12N15/11 ,  A61K35/76 ,  C12N9/22 ,  C12N15/86 ,  C12N15/861 ,  C12N15/90

CPC分类号： C12N15/11 ,  A61K35/76 ,  C12N9/22 ,  C12N15/86 ,  C12N15/8616 ,  C12N15/907 ,  C12N2310/20 ,  C12N2750/14143 ,  C12N2750/14171 ,  C12N2800/80

摘要： Aspects of the disclosure relate to recombinant gene editing complexes comprising a recombinant gene editing protein and guide RNA (gRNA) that specifically hybridizes to a region of a C90RF72 gene (e.g., a region flanking a G4C2 repeat or within a exonic region of the gene).