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1. 发明申请

US20190112600A1 CONDITIONAL PROTEIN TRANSLATION SWITCHES, CONDITIONAL GENE EXPRESSION SYSTEMS AND USES THEREOF 审中-公开
公开(公告)号：US20190112600A1
公开(公告)日：2019-04-18
申请号：US16157183
申请日：2018-10-11
申请人： Massachusetts Institute of Technology
发明人： Patrick J. Stern
IPC分类号： C12N15/11 , C12N15/85 , C12N15/63
CPC分类号： C12N15/111 , C12N15/09 , C12N15/635 , C12N15/67 , C12N15/85 , C12N2310/14 , C12N2320/30 , C12N2800/30 , C12N2830/50 , C12N2840/002 , C12N2840/102 , C12Q1/6897 , C12Q2521/507
摘要： Disclosed herein are protein translation switches and conditional gene expression systems that are compatible with retroviral and lentiviral gene delivery. The linking of a protein translation switch to a 3′ gene of interest suppresses translation of the gene of interest, and the alteration of the protein translation switch by DNA recombinase-mediated DNA recombination relieves the suppressed translation of the 3′ gene of interest. Also disclosed herein are methods of mimicking clinical pharmacology in a pre-clinical setting.

2. 发明申请

US20170202979A1 TERMINAL MODIFICATIONS OF POLYNUCLEOTIDES 审中-公开
公开(公告)号：US20170202979A1
公开(公告)日：2017-07-20
申请号：US15326266
申请日：2015-07-17
申请人： ModernaTX, Inc.
发明人： Tirtha CHAKRABORTY , Stephen G. HOGE
IPC分类号： A61K48/00 , A61K38/18 , C12N15/85 , C07K14/535 , C07K14/505 , C12N15/113 , A61K38/19 , C12N15/67
CPC分类号： A61K48/0066 , A61K38/1816 , A61K38/193 , C07H21/04 , C07K14/505 , C07K14/535 , C12N15/113 , C12N15/1136 , C12N15/67 , C12N15/85 , C12N2310/141 , C12N2310/3519 , C12N2840/102 , C12N2840/105
摘要： The present invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotides comprising at least one terminal modification.

3. 发明申请

US20160304903A1 PROMOTER-REGULATED DIFFERENTIATION-DEPENDENT SELF-DELETING CASSETTE 有权
公开(公告)号：US20160304903A1
公开(公告)日：2016-10-20
申请号：US15200832
申请日：2016-07-01
申请人： Regeneron Pharmaceuticals, Inc.
发明人： David Frendewey , Guochun Gong , Ka-Man Venus Lai , David M. Valenzuela
IPC分类号： C12N15/85 , C12N9/12 , C12N15/90 , C12N5/0735
CPC分类号： C12N15/85 , A01K67/0275 , A01K67/0276 , A01K2217/07 , A01K2217/075 , A01K2217/206 , A01K2227/105 , A01K2267/03 , C12N5/0606 , C12N9/1241 , C12N15/8509 , C12N15/873 , C12N15/907 , C12N2800/22 , C12N2800/30 , C12N2840/102 , C12Y207/07
摘要： Targeting constructs and methods of using them are provided for differentiation-dependent modification of nucleic acid sequences in cells and in non-human animals. Targeting constructs comprising a promoter operably linked to a recombinase are provided, wherein the promoter drives transcription of the recombinase in an differentiated cell but not an undifferentiated cell. Promoters include Blimp1, Prm1, Gata6, Gata4, Igf2, Lhx2, Lhx5, and Pax3. Targeting constructs with a cassette flanked on both sides by recombinase sites can be removed using a recombinase gene operably linked to a 3′-UTR that comprises a recognition site for an miRNA that is transcribed in undifferentiated cells but not in differentiated cells. The constructs may be included in targeting vectors, and can be used to automatically modify or excise a selection cassette from an ES cell, a non-human embryo, or a non-human animal.

4. 发明授权

US09284563B2 Stringent selectable markers 有权
标题翻译：严格的可选标记
公开(公告)号：US09284563B2
公开(公告)日：2016-03-15
申请号：US13378006
申请日：2010-06-15
申请人： Arie Pieter Otte , Henricus Johannes Maria Van Blokland , John Antonius Verhees
发明人： Arie Pieter Otte , Henricus Johannes Maria Van Blokland , John Antonius Verhees
IPC分类号： C12N15/65 , C12N15/67 , C12N15/52 , C12N15/85
CPC分类号： C12N15/65 , C12N15/52 , C12N15/67 , C12N15/85 , C12N2840/102 , C12N2840/206 , C12Y404/01001
摘要： The present invention relates to nucleic acid constructs comprising selectable marker genes in a multicistronic transcription unit for use in the generation and selection of eukaryotic host cells for expression of a gene product of interest. For increased stringency of selection, the coding sequence of the selectable marker may be directed preceded by a relatively short functional open reading frame to reduce the efficiency of translation of the selectable marker, and/or the amino acid sequence of the selectable marker may comprise one or more mutations that reduce the level of resistance provide by the mutated marker as compared to its wild type counterpart. The invention further relates to methods for generating eukaryotic host cells for expression of a gene product of interest, wherein these nucleic acid constructs are used, and to methods for producing a gene product of interest wherein thus generated host cells are applied.
摘要翻译：本发明涉及包含用于产生和选择用于表达感兴趣的基因产物的真核宿主细胞的多顺反子转录单位中的选择性标记基因的核酸构建体。为了增加选择的严格性，选择性标记的编码序列之前可以有较短的功能性开放阅读框，以降低选择性标记的翻译效率，和/或可选择标记的氨基酸序列可以包含一个或更多的突变，其降低与其野生型对应物相比由突变标记提供的抗性水平。本发明还涉及用于产生用于表达目标基因产物的真核宿主细胞的方法，其中使用这些核酸构建体，以及用于产生感兴趣的基因产物的方法，其中施用了由此产生的宿主细胞。

5. 发明授权

US09217155B2 Isolation of novel AAV'S and uses thereof 有权
标题翻译：分离新型AAV'S及其用途
公开(公告)号：US09217155B2
公开(公告)日：2015-12-22
申请号：US12686097
申请日：2010-01-12
申请人： Guangping Gao , Phillip D. Zamore
发明人： Guangping Gao , Phillip D. Zamore
IPC分类号： C12N15/86 , C12N15/85 , C12N15/11
CPC分类号： A61K48/0008 , A01K67/0275 , A01K2207/05 , A01K2217/058 , A01K2227/105 , A01K2267/03 , A01K2267/0331 , A61K9/0019 , A61K38/00 , A61K48/0058 , C12N7/00 , C12N15/111 , C12N15/113 , C12N15/8509 , C12N15/86 , C12N2015/8527 , C12N2310/13 , C12N2310/141 , C12N2320/32 , C12N2330/51 , C12N2710/10342 , C12N2750/14143 , C12N2750/14145 , C12N2820/002 , C12N2840/007 , C12N2840/102
摘要： The invention in some aspects relates to isolated nucleic acids, compositions, and kits useful for identifying adeno-associated viruses in cells. In some aspects, the invention provides kits and methods for producing somatic transgenic animal models using recombinant AAV (rAAV) to an animal having at least one transgene that expresses a small interfering nucleic acid or at least one binding site for a miRNA.
摘要翻译：本发明在一些方面涉及用于鉴定细胞中腺相关病毒的分离的核酸，组合物和试剂盒。在一些方面，本发明提供用于使用重组AAV（rAAV）产生体细胞转基因动物模型的试剂盒和方法，所述重组AAV（rAAV）具有至少一个表达小干扰核酸或至少一个miRNA结合位点的转基因。

6. 发明授权

US09051391B2 Method for expression of specific gene 有权
标题翻译：特异性基因表达方法
公开(公告)号：US09051391B2
公开(公告)日：2015-06-09
申请号：US12664133
申请日：2008-06-10
申请人： Junichi Mineno , Sachiko Okamoto , Risa Sumioka , Masanari Kitagawa , Hiroshi Shiku , Ikunoshin Kato
发明人： Junichi Mineno , Sachiko Okamoto , Risa Sumioka , Masanari Kitagawa , Hiroshi Shiku , Ikunoshin Kato
IPC分类号： C12P21/06 , C12N5/00 , C12N15/63 , C07K14/725
CPC分类号： C07K14/7051 , C12N15/85 , C12N2800/40 , C12N2840/102
摘要： Disclosed is a cell which can express a non-natural oligomeric protein, which has, introduced therein, a gene encoding an exogenous polypeptide corresponding to at least one endogenous polypeptide constituting a natural oligomeric protein, and in which the expression of the endogenous polypeptide is inhibited.
摘要翻译：公开了可以表达非天然寡聚蛋白质的细胞，其中引入了编码对应于构成天然寡聚蛋白质的至少一种内源多肽的外源多肽的基因，并且其中内源多肽的表达被抑制。

7. 发明申请

US20140363469A1 VIRAL ATTENUATION AND VACCINE PRODUCTION 审中-公开
标题翻译：病毒衰退和疫苗生产
公开(公告)号：US20140363469A1
公开(公告)日：2014-12-11
申请号：US14373195
申请日：2013-01-16
申请人： Alnylam Pharmaceuticals, Inc.
发明人： Rachel Meyers , Brian Bettencourt , Jamie Evan Wong , John M. Maraganore
IPC分类号： A61K39/245 , C12N7/00
CPC分类号： A61K39/245 , A61K39/00 , C12N7/00 , C12N2310/113 , C12N2310/141 , C12N2320/30 , C12N2320/32 , C12N2710/16622 , C12N2710/16634 , C12N2710/16662 , C12N2840/102
摘要： The present invention is directed to the generation of attenuated viruses or viral transcripts for the production of vaccines by incorporating microRNA binding sites within the viral target sequence of the pathogen.
摘要翻译：本发明涉及通过在病原体的病毒靶序列内并入微小RNA结合位点来产生用于生产疫苗的减毒病毒或病毒转录物。

8. 发明申请

US20140314704A1 Treatment of B Cell Lymphomas 审中-公开
标题翻译： B细胞淋巴瘤的治疗
公开(公告)号：US20140314704A1
公开(公告)日：2014-10-23
申请号：US14362005
申请日：2012-11-30
申请人： Senesco Technologies, Inc.
发明人： John E. Thompson
IPC分类号： A61K47/48 , A61K31/69 , A61K31/454 , A61K31/713 , A61K48/00
CPC分类号： A61K31/454 , A61K31/69 , A61K31/713 , A61K38/00 , A61K47/595 , A61K48/005 , C12N15/85 , C12N2840/102
摘要： Controlled-release formulations of carboxy-terminal C5a analogs (such as sustained-release formulations of the analogs), and their use in methods for treating and preventing an infection or a disease such as cancer, for directly killing microorganisms, for vaccine preparation, for inducing an immune response and for targeting antigen-presenting cells and other cells bearing a C5a receptor, are provided.
摘要翻译：羧基末端C5a类似物（例如类似物的缓释制剂）的控制释放制剂及其在治疗和预防感染或疾病如癌症的方法中的用途，用于直接杀死微生物，用于疫苗制备，用于疫苗制备诱导免疫应答并靶向抗原呈递细胞和其它具有C5a受体的细胞。

9. 发明申请

US20140189900A1 miRNA-REGULATED DIFFERENTIATION-DEPENDENT SELF-DELETING CASSETTE 有权
标题翻译： miRNA调控差异依赖性自我删除CASSETTE
公开(公告)号：US20140189900A1
公开(公告)日：2014-07-03
申请号：US14176484
申请日：2014-02-10
申请人： Regeneron Pharmaceuticals, Inc.
发明人： David Frendewey , David Jonathan Heslin , Ka-Man Venus Lai , David M. Valenzuela
IPC分类号： C12N15/85
CPC分类号： C12N15/85 , A01K67/0275 , A01K67/0276 , A01K2217/07 , A01K2217/075 , A01K2217/206 , A01K2227/105 , A01K2267/03 , C12N5/0606 , C12N9/1241 , C12N15/8509 , C12N15/873 , C12N15/907 , C12N2800/22 , C12N2800/30 , C12N2840/102 , C12Y207/07
摘要： Targeting constructs and methods of using them are provided for differentiation-dependent modification of nucleic acid sequences in cells and in non-human animals. Targeting constructs comprising a promoter operably linked to a recombinase are provided, wherein the promoter drives transcription of the recombinase in an differentiated cell but not an undifferentiated cell. Promoters include Blimp1, Prm1, Gata6, Gata4, Igf2, Lhx2, Lhx5, and Pax3. Targeting constructs with a cassette flanked on both sides by recombinase sites can be removed using a recombinase gene operably linked to a 3′-UTR that comprises a recognition site for an miRNA that is transcribed in undifferentiated cells but not in differentiated cells. The constructs may be included in targeting vectors, and can be used to automatically modify or excise a selection cassette from an ES cell, a non-human embryo, or a non-human animal.
摘要翻译：提供靶向构建体和使用它们的方法用于细胞和非人动物中核酸序列的分化依赖性修饰。提供了包含与重组酶可操作地连接的启动子的靶向构建体，其中所述启动子驱动分化细胞中但不是未分化细胞的重组酶的转录。启动子包括Blimp1，Prm1，Gata6，Gata4，Igf2，Lhx2，Lhx5和Pax3。可以使用可操作地连接到3'-UTR的重组酶基因来除去具有通过重组酶位点两侧的盒的靶向构建体，其包含在未分化细胞中但不在分化细胞中转录的miRNA的识别位点。构建体可以包括在靶向载体中，并且可以用于自动修饰或从ES细胞，非人胚胎或非人动物中切除选择盒。

10. 发明授权

US08697851B2 MiRNA-regulated differentiation-dependent self-deleting cassette 有权
标题翻译： MiRNA调节的分化依赖性自我删除盒
公开(公告)号：US08697851B2
公开(公告)日：2014-04-15
申请号：US13692764
申请日：2012-12-03
申请人： Regeneron Pharmaceuticals, Inc.
发明人： David Frendewey , David Jonathan Heslin , Ka-Man Venus Lai , David M. Valenzuela
IPC分类号： C07H21/04 , C12N5/07 , C12N5/12 , C12N15/00 , C12N15/87
CPC分类号： C12N15/85 , A01K67/0275 , A01K67/0276 , A01K2217/07 , A01K2217/075 , A01K2217/206 , A01K2227/105 , A01K2267/03 , C12N5/0606 , C12N9/1241 , C12N15/8509 , C12N15/873 , C12N15/907 , C12N2800/22 , C12N2800/30 , C12N2840/102 , C12Y207/07
摘要： Targeting constructs and methods of using them are provided for differentiation-dependent modification of nucleic acid sequences in cells and in non-human animals. Targeting constructs comprising a promoter operably linked to a recombinase are provided, wherein the promoter drives transcription of the recombinase in an differentiated cell but not an undifferentiated cell. Promoters include Blimp1, Prm1, Gata6, Gata4, Igf2, Lhx2, Lhx5, and Pax3. Targeting constructs with a cassette flanked on both sides by recombinase sites can be removed using a recombinase gene operably linked to a 3′-UTR that comprises a recognition site for an miRNA that is transcribed in undifferentiated cells but not in differentiated cells. The constructs may be included in targeting vectors, and can be used to automatically modify or excise a selection cassette from an ES cell, a non-human embryo, or a non-human animal.
摘要翻译：提供靶向构建体和使用它们的方法用于细胞和非人动物中核酸序列的分化依赖性修饰。提供了包含与重组酶可操作地连接的启动子的靶向构建体，其中所述启动子驱动分化细胞中但不是未分化细胞的重组酶的转录。启动子包括Blimp1，Prm1，Gata6，Gata4，Igf2，Lhx2，Lhx5和Pax3。可以使用可操作地连接到3'-UTR的重组酶基因来除去具有通过重组酶位点两侧的盒的靶向构建体，其包含在未分化细胞中但不在分化细胞中转录的miRNA的识别位点。构建体可以包括在靶向载体中，并且可以用于自动修饰或从ES细胞，非人胚胎或非人动物中切除选择盒。

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