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公开(公告)号:US08147823B2
公开(公告)日:2012-04-03
申请号:US12832282
申请日:2010-07-08
申请人: Gregory M. Acland , Gustavo D. Aguirre , Jean Bennett , William W. Hauswirth , Samuel G. Jacobson , Albert M. Maguire
发明人: Gregory M. Acland , Gustavo D. Aguirre , Jean Bennett , William W. Hauswirth , Samuel G. Jacobson , Albert M. Maguire
IPC分类号: A61K48/00 , C12N15/12 , C12N15/861
CPC分类号: A61K48/0058 , A61K9/0048 , A61K31/70 , A61K38/00 , A61K38/465 , A61K38/51 , A61K38/52 , A61K48/00 , A61K48/005 , A61K48/0075 , C07K14/705 , C12N7/00 , C12N15/86 , C12N15/8645 , C12N2750/14132 , C12N2750/14142 , C12N2750/14143 , C12N2750/14171 , C12N2830/008 , C12N2830/85 , C12N2840/203 , C12Y301/01064
摘要: A method for treating an ocular disorder characterized by the defect or absence of a normal gene in the ocular cells of a human or animal subject involves administering to the subject by subretinal injection an effective amount of a recombinant adeno-associated virus carrying a nucleic acid sequence encoding the normal gene under the control of a promoter sequence which expresses the product of the gene in the ocular cells. The ocular cells are preferably retinal pigment epithelial (RPE) cells, and the gene is preferably an RPE-specific gene, e.g., RPE65. The promoter is one that can express the gene product in the RPE cells. Compositions for subretinal administration are useful in this method.
摘要翻译: 用于治疗人或动物对象的眼细胞中缺陷或不存在正常基因的眼部疾病的方法包括通过视网膜下注射给予受试者有效量的携带核酸序列的重组腺相关病毒 编码在表达基因在眼细胞中的产物的启动子序列控制下的正常基因。 眼细胞优选为视网膜色素上皮细胞(RPE),该基因优选为RPE特异性基因,例如RPE65。 启动子是可以在RPE细胞中表达基因产物的启动子。 视网膜下给药的组合物在该方法中是有用的。
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公开(公告)号:US20090074723A1
公开(公告)日:2009-03-19
申请号:US12253955
申请日:2008-10-18
申请人: Gregory M. Acland , Gustavo D. Aguirre , Jean Bennett , William W. Hauswirth , Samuel G. Jacobson , Albert M. Maguire
发明人: Gregory M. Acland , Gustavo D. Aguirre , Jean Bennett , William W. Hauswirth , Samuel G. Jacobson , Albert M. Maguire
IPC分类号: A61K48/00 , A61K31/7088 , A61K35/12 , A61K35/76 , A61P27/02
CPC分类号: A61K48/0058 , A61K9/0048 , A61K31/70 , A61K38/00 , A61K38/465 , A61K38/51 , A61K38/52 , A61K48/00 , A61K48/005 , A61K48/0075 , C07K14/705 , C12N7/00 , C12N15/86 , C12N15/8645 , C12N2750/14132 , C12N2750/14142 , C12N2750/14143 , C12N2750/14171 , C12N2830/008 , C12N2830/85 , C12N2840/203 , C12Y301/01064
摘要: A method for treating an ocular disorder characterized by the defect or absence of a normal gene in the ocular cells of a human or animal subject involves administering to the subject by subretinal injection an effective amount of a recombinant adeno-associated virus carrying a nucleic acid sequence encoding the normal gene under the control of a promoter sequence which expresses the product of the gene in the ocular cells. The ocular cells are preferably retinal pigment epithelial (RPE) cells, and the gene is preferably an RPE-specific gene, e.g., RPE65. The promoter is one that can express the gene product in the RPE cells. Compositions for subretinal administration are useful in this method.
摘要翻译: 用于治疗人或动物对象的眼细胞中缺陷或不存在正常基因的眼部疾病的方法包括通过视网膜下注射给予受试者有效量的携带核酸序列的重组腺相关病毒 编码在表达基因在眼细胞中的产物的启动子序列控制下的正常基因。 眼细胞优选为视网膜色素上皮细胞(RPE),该基因优选为RPE特异性基因,例如RPE65。 启动子是可以在RPE细胞中表达基因产物的启动子。 视网膜下给药的组合物在该方法中是有用的。
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公开(公告)号:US20120225930A1
公开(公告)日:2012-09-06
申请号:US13406666
申请日:2012-02-28
申请人: Gregory M. Acland , Gustavo D. Aguirre , Jean Bennett , William W. Hauswirth , Samuel G. Jacobson , Albert M. Maguire
发明人: Gregory M. Acland , Gustavo D. Aguirre , Jean Bennett , William W. Hauswirth , Samuel G. Jacobson , Albert M. Maguire
IPC分类号: A61K31/711 , A61P27/02
CPC分类号: A61K48/0058 , A61K9/0048 , A61K31/70 , A61K38/00 , A61K38/465 , A61K38/51 , A61K38/52 , A61K48/00 , A61K48/005 , A61K48/0075 , C07K14/705 , C12N7/00 , C12N15/86 , C12N15/8645 , C12N2750/14132 , C12N2750/14142 , C12N2750/14143 , C12N2750/14171 , C12N2830/008 , C12N2830/85 , C12N2840/203 , C12Y301/01064
摘要: A method for treating an ocular disorder characterized by the defect or absence of a normal gene in the ocular cells of a human or animal subject involves administering to the subject by subretinal injection an effective amount of a recombinant adeno-associated virus carrying a nucleic acid sequence encoding the normal gene under the control of a promoter sequence which expresses the product of the gene in the ocular cells. The ocular cells are preferably retinal pigment epithelial (RPE) cells, and the gene is preferably an RPE-specific gene, e.g., RPE65. The promoter is one that can express the gene product in the RPE cells. Compositions for subretinal administration are useful in this method.
摘要翻译: 用于治疗人或动物对象的眼细胞中缺陷或不存在正常基因的眼部疾病的方法包括通过视网膜下注射给予受试者有效量的携带核酸序列的重组腺相关病毒 编码在表达基因在眼细胞中的产物的启动子序列控制下的正常基因。 眼细胞优选为视网膜色素上皮细胞(RPE),该基因优选为RPE特异性基因,例如RPE65。 启动子是可以在RPE细胞中表达基因产物的启动子。 视网膜下给药的组合物在该方法中是有用的。
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公开(公告)号:US20100272688A1
公开(公告)日:2010-10-28
申请号:US12832282
申请日:2010-07-08
申请人: Gregory M. Acland , Gustavo D. Aguirre , Jean Bennett , William W. Hauswirth , Samuel G. Jacobson , Albert M. Maguire
发明人: Gregory M. Acland , Gustavo D. Aguirre , Jean Bennett , William W. Hauswirth , Samuel G. Jacobson , Albert M. Maguire
CPC分类号: A61K48/0058 , A61K9/0048 , A61K31/70 , A61K38/00 , A61K38/465 , A61K38/51 , A61K38/52 , A61K48/00 , A61K48/005 , A61K48/0075 , C07K14/705 , C12N7/00 , C12N15/86 , C12N15/8645 , C12N2750/14132 , C12N2750/14142 , C12N2750/14143 , C12N2750/14171 , C12N2830/008 , C12N2830/85 , C12N2840/203 , C12Y301/01064
摘要: A method for treating an ocular disorder characterized by the defect or absence of a normal gene in the ocular cells of a human or animal subject involves administering to the subject by subretinal injection an effective amount of a recombinant adeno-associated virus carrying a nucleic acid sequence encoding the normal gene under the control of a promoter sequence which expresses the product of the gene in the ocular cells. The ocular cells are preferably retinal pigment epithelial (RPE) cells, and the gene is preferably an RPE-specific gene, e.g., RPE65. The promoter is one that can express the gene product in the RPE cells. Compositions for subretinal administration are useful in this method.
摘要翻译: 用于治疗人或动物对象的眼细胞中缺陷或不存在正常基因的眼部疾病的方法包括通过视网膜下注射给予受试者有效量的携带核酸序列的重组腺相关病毒 编码在表达基因在眼细胞中的产物的启动子序列控制下的正常基因。 眼细胞优选为视网膜色素上皮细胞(RPE),该基因优选为RPE特异性基因,例如RPE65。 启动子是可以在RPE细胞中表达基因产物的启动子。 视网膜下给药的组合物在该方法中是有用的。
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公开(公告)号:US5012815A
公开(公告)日:1991-05-07
申请号:US533544
申请日:1990-06-05
IPC分类号: A61B7/04
CPC分类号: A61B7/04
摘要: A system of generating a spectral phonocardiogram which summarizes time-dependent changes in the heart sounds throughout the heart cycle. The system is based on the projection of spectral surfaces of the Fourier transform of heart sounds as a function of time and is a useful diagnostic tool both for a cardiologist and a general practitioner. Permanent copies of the spectral phonocardiograms can provide useful records for monitoring the development of heart disease in a given individual. The system provides a useful means for rapid screening of large groups of people for heart disease by non-specialists in cardiology. A variant of the system provides automated computer diagnosis of the probable nature of the heart disease.
摘要翻译: 产生频谱心电图的系统,其总结心脏周期中心音的时间依赖性变化。 该系统基于心音的傅立叶变换的时间的函数的投影,并且是心脏病学家和全科医生的有用的诊断工具。 光谱心电图的永久性拷贝可以为监测给定个体心脏病发展提供有用的记录。 该系统为心脏病专家的非专家快速筛查大量心脏病患者提供了有用的手段。 该系统的变体提供对心脏病的可能性质的自动计算机诊断。
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6.
公开(公告)号:US09249425B2
公开(公告)日:2016-02-02
申请号:US14117312
申请日:2012-05-16
IPC分类号: C07K14/435 , C12N15/86 , C12N15/35 , C12N15/864
CPC分类号: C12N7/00 , C07K14/435 , C12N15/86 , C12N2750/14111 , C12N2750/14121 , C12N2750/14141 , C12N2750/14143 , C12N2750/14152 , C12N2800/107 , C12N2830/60 , C12N2830/90
摘要: Proviral plasmids contain a modular gene expression cassette with one or a combination of (i) a wildtype 5′ AAV2 ITR sequence flanked by unique restriction sites that permit ready removal or replacement of said ITR; (ii) a promoter flanked by unique restriction sites that permit ready removal or replacement of the entire promoter sequence; (iii) a polylinker sequence that permits insertion of a gene coding sequence without modification thereof, wherein the gene is operatively linked to, and under the regulatory control of, the aforementioned promoter; (iv) a bovine growth hormone polyadenylation sequence flanked by unique restriction sites that permit ready removal or replacement of said polyA sequence; and (v) a wildtype 3′ AAV2 ITR sequence flanked by unique restriction sites that permit ready removal or replacement of the 3′ ITR. These plasmids enable rapid manipulation of the components of the cassette, e.g., rapid mutation and/or replacement of any component, and thereby increase the efficiency of recombinant viral vector, e.g., rAAV, production.
摘要翻译: 丙型肝炎病毒质粒包含一个或多个组合的模块化基因表达盒,(i)野生型5'AAV2 ITR序列,其侧翼是唯一的限制性位点,允许准备移除或替换所述ITR; (ii)侧翼为独特的限制性位点的启动子,其允许准备去除或置换整个启动子序列; (iii)允许插入基因编码序列而无需修饰的多接头序列,其中所述基因与上述启动子有效连接并在其调控下控制; (iv)两侧有唯一限制性位点的牛生长激素多聚腺苷酸化序列,其允许准备移除或替换所述polyA序列; 和(v)野生型3'AAV2 ITR序列,其侧翼是唯一的限制性位点,允许准备移除或替换3'ITR。 这些质粒能够快速操作盒的组分,例如任何组分的快速突变和/或置换,从而提高重组病毒载体如rAAV产生的效率。
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7.
公开(公告)号:US20140087444A1
公开(公告)日:2014-03-27
申请号:US14117312
申请日:2012-05-16
IPC分类号: C12N15/86
CPC分类号: C12N7/00 , C07K14/435 , C12N15/86 , C12N2750/14111 , C12N2750/14121 , C12N2750/14141 , C12N2750/14143 , C12N2750/14152 , C12N2800/107 , C12N2830/60 , C12N2830/90
摘要: Proviral plasmids contain a modular gene expression cassette with one or a combination of (i) a wildtype 5′ AAV2 ITR sequence flanked by unique restriction sites that permit ready removal or replacement of said ITR; (ii) a promoter flanked by unique restriction sites that permit ready removal or replacement of the entire promoter sequence; (iii) a polylinker sequence that permits insertion of a gene coding sequence without modification thereof, wherein the gene is operatively linked to, and under the regulatory control of, the aforementioned promoter; (iv) a bovine growth hormone polyadenylation sequence flanked by unique restriction sites that permit ready removal or replacement of said polyA sequence; and (v) a wildtype 3′ AAV2 ITR sequence flanked by unique restriction sites that permit ready removal or replacement of the 3′ ITR. These plasmids enable rapid manipulation of the components of the cassette, e.g., rapid mutation and/or replacement of any component, and thereby increase the efficiency of recombinant viral vector, e.g., rAAV, production.
摘要翻译: 丙型肝炎病毒质粒包含一个或多个组合的模块化基因表达盒,(i)野生型5'AAV2 ITR序列,其侧翼是唯一的限制性位点,允许准备移除或替换所述ITR; (ii)侧翼为独特的限制性位点的启动子,其允许准备去除或置换整个启动子序列; (iii)允许插入基因编码序列而无需修饰的多接头序列,其中所述基因与上述启动子有效连接并在其调控下控制; (iv)两侧有唯一限制性位点的牛生长激素多聚腺苷酸化序列,其允许准备移除或替换所述polyA序列; 和(v)野生型3'AAV2 ITR序列,其侧翼是唯一的限制性位点,允许准备移除或替换3'ITR。 这些质粒能够快速操作盒的组分,例如任何组分的快速突变和/或置换,从而提高重组病毒载体如rAAV产生的效率。
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公开(公告)号:US20120244127A1
公开(公告)日:2012-09-27
申请号:US13499212
申请日:2010-09-30
IPC分类号: A61K35/76 , C12N5/10 , A61P13/12 , C12N15/864
CPC分类号: A61K48/0075 , A61K48/00 , C12N7/00 , C12N15/86 , C12N2710/10032 , C12N2750/14143
摘要: A method for enhancing repair of damaged mammalian tubular epithelial cells involves delivering to the tubular epithelial cells of a subject in need thereof a composition comprising an adeno-associated virus (AAV) comprising an AAV capsid having an amino acid sequence of a selected AAV serotype, and a minigene having AAV inverted terminal repeats and a Sec10 gene operatively linked to regulatory sequences that direct expression of Sec10 in the epithelial cells. In one embodiment, delivery is accomplished by retrograde intrauretal injection. In an embodiment the AAV vector includes a capsid of AAV serotype 2/8. Therapeutic compositions containing such AAV are provided.
摘要翻译: 增强损伤的哺乳动物肾小管上皮细胞修复的方法涉及向有需要的对象的管状上皮细胞递送包含腺伴随病毒(AAV)的组合物,其包含具有所选AAV血清型氨基酸序列的AAV衣壳, 和具有AAV反向末端重复的小基因和与指导Sec10在上皮细胞中表达的调节序列可操作地连接的Sec10基因。 在一个实施方案中,通过逆行心内注射实现递送。 在一个实施方案中,AAV载体包括AAV血清型2/8的衣壳。 提供含有这种AAV的治疗组合物。
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公开(公告)号:US20220096658A1
公开(公告)日:2022-03-31
申请号:US17416311
申请日:2019-12-20
申请人: Wade W. Chien , Jean Bennett
发明人: Wade W. Chien , Jean Bennett
摘要: Provided herein are adeno-associated viruses and methods for using same to treat or prevent disorders that affect the inner ear of a subject.
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公开(公告)号:US20100297084A1
公开(公告)日:2010-11-25
申请号:US12601898
申请日:2008-05-30
申请人: Jean Bennett , Joshua Lipschutz
发明人: Jean Bennett , Joshua Lipschutz
摘要: This invention provides methods for transducing a ciliated cell with a recombinant serotype 2 adeno-associated virus (AAV) vector. Additionally, the invention provides methods of treating diseases associated with a mutated gene by transducing a ciliated cell with a recombinant serotype 2 AAV vector containing a corrective transgene.
摘要翻译: 本发明提供了用重组血清型2腺相关病毒(AAV)载体转导纤毛细胞的方法。 另外,本发明提供了通过用含有修复转基因的重组血清型2 AAV载体转导纤毛细胞来治疗与突变基因相关的疾病的方法。
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