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1. 发明申请

WO2008021393A3 ORTHOTOPIC, CONTROLLABLE, AND GENETICALLY TRACTABLE NON-HUMAN ANIMAL MODEL FOR CANCER 审中-公开
标题翻译： ORCOTOPIC，可控制和可遗传的可触发的非人类动物模型
公开(公告)号：WO2008021393A3
公开(公告)日：2008-11-20
申请号：PCT/US2007018061
申请日：2007-08-15
申请人： COLD SPRING HARBOR LAB , LOWE SCOTT W , HANNON GREGORY J , ZENDER LARS , XUE WEN , DICKINS ROSS
发明人： LOWE SCOTT W , HANNON GREGORY J , ZENDER LARS , XUE WEN , DICKINS ROSS
IPC分类号： G01N33/00 , A01K67/00
CPC分类号： A01K67/0271 , A01K2267/0331 , C07K14/82 , C12N15/1135 , C12N2310/111 , C12N2310/14 , C12N2310/53 , C12N2320/50 , C12N2799/027 , C12N2830/006
摘要： This invention provides a genetically tractable in situ non-human animal model for hepatocellular carcinoma. The model is useful, inter alia, in understanding the molecular mechanisms of liver cancer, in understanding the genetic alterations {e.g., in oncogenes and tumor suppressor genes) that lead to chemoresistance or poor prognosis, and in identifying and evaluating new therapies against hepatocellular carcinomas. The liver cancer model of this invention is made by altering hepatocytes to increase oncogene expression, to reduce tumor suppressor gene expression or both, preferably by inducible, reversible, and/or tissue specific expression of double-stranded RNA molecules that interfere with the expression of a target gene, and by transplanting the resulting hepatocytes into a recipient non-human animal. The invention further provides a method to treat cancer involving cooperative interactions between a tumor cell senescence program and the innate immune system.
摘要翻译：本发明提供了用于肝细胞癌的遗传易处理的非人动物模型。该模型尤其有助于了解肝癌的分子机制，了解导致化疗耐药性或预后不良的遗传改变（例如，致癌基因和肿瘤抑制基因），以及鉴定和评估针对肝细胞癌的新疗法。本发明的肝癌模型通过改变肝细胞以增加癌基因表达，减少肿瘤抑制基因表达或两者，优选通过诱导的，可逆的和/或组织特异性表达的双链RNA分子来制备，所述双链RNA分子干扰表达靶基因，并将所得肝细胞移植到受体非人动物中。本发明还提供了一种治疗涉及肿瘤细胞衰老程序与先天免疫系统之间协同作用的癌症的方法。

2. 发明申请

WO2007053184A3 METHODS FOR PRODUCING MICRORNAS 审中-公开
标题翻译：生产微生物的方法
公开(公告)号：WO2007053184A3
公开(公告)日：2007-07-12
申请号：PCT/US2006021062
申请日：2006-05-31
申请人： COLD SPRING HARBOR LAB , DICKINS ROSS , HANNON GREGORY J , LOWE SCOTT W
发明人： DICKINS ROSS , HANNON GREGORY J , LOWE SCOTT W
IPC分类号： A01K67/02 , A61K31/7088 , A61K48/00 , C12N5/10 , C12N5/16 , C12N15/11 , C12N15/113 , C12N15/79 , C12N15/85 , C12N15/90
CPC分类号： A01K67/0271 , A01K67/0275 , A01K2217/05 , A01K2217/20 , A01K2227/105 , A01K2267/03 , A01K2267/0331 , C07K14/4746 , C07K14/82 , C12N15/111 , C12N15/1135 , C12N15/8509 , C12N2310/111 , C12N2310/14 , C12N2310/53 , C12N2320/50 , C12N2330/30 , C12N2799/027 , C12N2800/30 , C12N2830/003 , C12N2830/006 , C12N2830/008 , C12N2840/203
摘要： The invention relates to recombinant vectors for inducible and/or tissue specific expression of double-stranded RNA molecules that interfere with the expression of a target gene. In certain embodiments, the invention relates to the use of Tet (tetracycline)-responsive RNA Polymerase II (Pol II) promoters (e.g., TetON or TetOFF) to direct inducible knockdown in certain cells of an integrated or an endogenous gene, such as p53. The invention also relates to a method for producing transgenic animals (e.g., mice) expressing inducible (such as tetracycline-regulated), reversible, and/or tissue-specific double-stranded RNA molecules that interfere with the expression of a target gene.
摘要翻译：本发明涉及用于诱导和/或组织特异性表达干扰靶基因表达的双链RNA分子的重组载体。在某些实施方案中，本发明涉及Tet（四环素） - 反应性RNA聚合酶II（Pol II）启动子（例如TetON或TetOFF）在整合或内源基因如p53的某些细胞中的诱导性敲低的用途。本发明还涉及产生干扰靶基因表达的诱导型（如四环素调节），可逆性和/或组织特异性双链RNA分子的转基因动物（例如小鼠）的方法。

3. 发明申请

WO2004029219A3 CELL-BASED RNA INTERFERENCE AND RELATED METHODS AND COMPOSITIONS 审中-公开
标题翻译：基于细胞的RNA干扰及相关方法和组合物
公开(公告)号：WO2004029219A3
公开(公告)日：2004-07-01
申请号：PCT/US0330901
申请日：2003-09-29
申请人： COLD SPRING HARBOR LAB , FRIDMAN JORDAN , HANNON GREGORY J , HEMANN MICHAEL , LOWE SCOTT W , PADDISON PATRICK J , ZILFOU JACK , DICKINS ROSS , CARMELL MICHELLE A , ROSENQUIST THOMAS A
发明人： FRIDMAN JORDAN , HANNON GREGORY J , HEMANN MICHAEL , LOWE SCOTT W , PADDISON PATRICK J , ZILFOU JACK , DICKINS ROSS , CARMELL MICHELLE A , ROSENQUIST THOMAS A
IPC分类号： A61K48/00 , C12N15/11 , C12N15/113 , C12Q1/68 , A01N43/04 , A61K31/07 , C07H21/04
CPC分类号： C12N15/1135 , A61K48/00 , C12N15/111 , C12N15/1137 , C12N2310/111 , C12N2310/14 , C12N2310/53 , C12N2330/30 , C12N2330/31
摘要： The invention provides, among other things, methods for performing RNA interference in stem cells and methods for using the stem cells in vivo.
摘要翻译：本发明尤其提供了用于在干细胞中进行RNA干扰的方法以及在体内使用干细胞的方法。

4. 发明申请

WO2007139985A3 COOPERATING ONCOGENES IN CANCER 审中-公开
标题翻译：癌症合作癌症
公开(公告)号：WO2007139985A3
公开(公告)日：2008-07-31
申请号：PCT/US2007012592
申请日：2007-05-23
申请人： COLD SPRING HARBOR LAB , ZENDER LARS , LOWE SCOTT W , SPECTOR MONA S , XUE WEN
发明人： ZENDER LARS , LOWE SCOTT W , SPECTOR MONA S , XUE WEN
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , A01K2217/05 , A01K2267/0331 , C07K14/4747 , C07K14/82 , C12N2510/04 , C12Q2600/106 , C12Q2600/136 , C12Q2600/178
摘要： This invention provides methods of diagnosis, drug screening, and treatment based on the discovery that cIAP1 and Yap are co-amplified oncogenes that cooperate to contribute to oncogenesis and tumor maintenance.
摘要翻译：本发明基于cIAP1和Yap是共同扩增的致癌基因的发现提供了诊断，药物筛选和治疗的方法，所述致癌基因协作促成肿瘤发生和肿瘤维持。

5. 发明申请

WO2007139985A9 COOPERATING ONCOGENES IN CANCER 审中-公开
标题翻译：癌症合作关键
公开(公告)号：WO2007139985A9
公开(公告)日：2008-01-17
申请号：PCT/US2007012592
申请日：2007-05-23
申请人： COLD SPRING HARBOR LAB , ZENDER LARS , LOWE SCOTT W , SPECTOR MONA S , XUE WEN
发明人： ZENDER LARS , LOWE SCOTT W , SPECTOR MONA S , XUE WEN
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , A01K2217/05 , A01K2267/0331 , C07K14/4747 , C07K14/82 , C12N2510/04 , C12Q2600/106 , C12Q2600/136 , C12Q2600/178
摘要： This invention provides methods of diagnosis, drug screening, and treatment based on the discovery that cIAP1 and Yap are co-amplified oncogenes that cooperate to contribute to oncogenesis and tumor maintenance.
摘要翻译：本发明提供了诊断，药物筛选和治疗的方法，基于以下发现，cIAP1和Yap是共同扩增癌基因，其协作以有助于肿瘤发生和肿瘤维持。

6. 发明申请

WO2008115556A3 IDENTIFICATION OF GENETIC ALTERATIONS THAT MODULATE DRUG SENSITIVITY IN CANCER TREATMENTS 审中-公开
标题翻译：确定癌症治疗药物敏感性的遗传变异的鉴定
公开(公告)号：WO2008115556A3
公开(公告)日：2008-12-18
申请号：PCT/US2008003691
申请日：2008-03-19
申请人： COLD SPRING HARBOR LAB , LOWE SCOTT W , HEMANN MICHAEL , HANNON GREGORY J , BURGESS DARREN
发明人： LOWE SCOTT W , HEMANN MICHAEL , HANNON GREGORY J , BURGESS DARREN
IPC分类号： G01N33/567
CPC分类号： G01N33/5011 , C12N15/1079 , C12N15/111 , C12N15/113 , C12N15/1137 , C12N2310/14 , C12N2320/12 , C12N2320/31 , C12N2330/31 , C12Y599/01003
摘要： This invention features methods of identifying genetic alterations that can modulate cancer cells' sensitivity to an anti-cancer drug. Information on such genetic alterations can be used to predict cancer therapeutic outcomes and to stratify patient populations to maximize therapeutic efficacy.
摘要翻译：本发明的特征在于鉴定可调节癌细胞对抗癌药物的敏感性的遗传改变的方法。关于这种遗传改变的信息可用于预测癌症治疗结果并分层患者群体以最大化治疗功效。

7. 发明申请

WO2009055724A3 HIGH THROUGHPUT METHODS FOR FUNCTIONALLY DETERMINING RNA INTERFERENCE EFFICIENCY 审中-公开
标题翻译：用于功能测定RNA干扰效率的高通量方法
公开(公告)号：WO2009055724A3
公开(公告)日：2009-06-11
申请号：PCT/US2008081193
申请日：2008-10-24
申请人： COLD SPRING HARBOR LAB , FELLMANN CHRISTOF , LOWE SCOTT W , HANNON GREGORY J , ZUBER JOHANNES EKKEHART
发明人： FELLMANN CHRISTOF , LOWE SCOTT W , HANNON GREGORY J , ZUBER JOHANNES EKKEHART
IPC分类号： C12Q1/68 , C12N15/63
CPC分类号： C12Q1/6897 , C12N15/1086 , C12N15/113 , C12N15/85 , C12N2310/14
摘要： Provided is a single construct combining a sequence encoding an RNAi molecule, a sequence encoding a reporter, and a target sequence specific for the RNAi molecule. The construct can be used to determine the potency of the encoded RNAi molecule in a direct and unbiased way. These results can be used to inform the design of potent RNAi molecules of various types and can be extended to several other applications, including: (1) generation of tiled libraries comprising every possible RNAi molecule-encoding sequence for a given gene target; (2) large-scale parallel validation of RNAi molecules targeting many genes to generate validated RNAi molecule-encoding libraries; (3) experimental comparison of design algorithms and strategies; and (4) investigation of RNAi biology in target site mutagenesis assays by screening pools containing single nucleotide changes in target sites and/or in the RNAi molecule to identify the most relevant sequence characteristics of potent RNAi-target site predictions.
摘要翻译：提供了组合编码RNAi分子的序列，编码报道分子的序列和对RNAi分子特异的靶序列的单一构建体。该构建体可以用于以直接和公正的方式确定编码的RNAi分子的效力。这些结果可用于通知各种有效的RNAi分子的设计，并可扩展到其他几个应用，包括：（1）生成包含给定基因靶标的每个可能的RNAi分子编码序列的平铺文库; （2）针对许多基因的RNAi分子的大规模并行验证以产生经验证的RNAi分子编码文库; （3）设计算法和策略的实验比较; 和（4）通过在靶位点和/或RNAi分子中含有单核苷酸变化的筛选池来检测靶位点诱变测定中的RNAi生物学，以鉴定有效的RNAi靶位点预测的最相关的序列特征。

8. 发明申请

WO2008137862A2 METHODS OF USING MIR34 AS A BIOMARKER FOR TP53 FUNCTIONAL STATUS 审中-公开
标题翻译：使用MIR34作为生物标记物用于TP53功能状态的方法
公开(公告)号：WO2008137862A2
公开(公告)日：2008-11-13
申请号：PCT/US2008062681
申请日：2008-05-05
申请人： ROSETTA INPHARMATICS LLC , COLD SPRING HARBOR LAB , LINSLEY PETER S , LIM LEE P , CLEARY MICHELE A , JACKSON AIMEE L , BURCHARD JULJA , MAGNUS JILL F , HANNON GREGORY J , HE LIN , LOWE SCOTT W , HE XINGYUE
发明人： LINSLEY PETER S , LIM LEE P , CLEARY MICHELE A , JACKSON AIMEE L , BURCHARD JULJA , MAGNUS JILL F , HANNON GREGORY J , HE LIN , LOWE SCOTT W , HE XINGYUE
IPC分类号： C12Q1/68 , G06F19/00
CPC分类号： C12N15/113 , C12N15/111 , C12N2310/14 , C12N2310/141 , C12N2320/53 , C12Q1/6886 , C12Q2600/136 , C12Q2600/158 , C12Q2600/178
摘要： In one aspect, the invention generally relates to use of miR-34 as a biomarker to estimate TP53 function in a cell. In another aspect, the invention generally relates to multiple uses of miR-34 and siRNAs functionally and structurally related to miR-34 for the treatment of cancer.
摘要翻译：一方面，本发明一般涉及miR-34作为生物标志物来估计细胞中TP53功能的用途。在另一方面，本发明一般涉及miR-34和siRNA在功能上和结构上与miR-34相关的多种用途，用于治疗癌症。

9. 发明申请

WO2006074186A3 DEVELOPMENT AND USE OF A NEW ORTHOTOPIC GENETICALLY TRACTABLE NON-HUMAN ANIMAL MODEL FOR LIVER CANCER 审中-公开
标题翻译：开发和使用新型OROTOTOPIC可遗传的非人类动物模型用于肝癌
公开(公告)号：WO2006074186A3
公开(公告)日：2007-07-12
申请号：PCT/US2006000119
申请日：2006-01-03
申请人： COLD SPRING HARBOR LAB , ZENDER LARS , LOWE SCOTT W , SPECTOR MONA S
发明人： ZENDER LARS , LOWE SCOTT W , SPECTOR MONA S
IPC分类号： A01K67/027 , C12N5/06
CPC分类号： A01K67/0271 , A01K2227/105 , A01K2267/0331 , C07K14/4747 , C12N2510/04 , C12N2517/02 , C12N2799/027 , G01N33/57438 , G01N2800/52
摘要： This invention provides a genetically tractable in situ non-human animal model for hepatocellular carcinoma. The model is useful, inter alia, in understanding the molecular mechanisms of liver cancer, in understanding the genetic alterations that lead to chemoresistance or poor prognosis, and in identifying and evaluating new therapies against hepatocellular carcinomas. The liver cancer model of this invention is made by altering hepatocytes to increase oncogene expression, to reduce tumor suppressor gene expression or both and by transplanting the resulting hepatocytes into a recipient non-human animal.
摘要翻译：本发明提供了用于肝细胞癌的遗传易处理的非人动物模型。该模型除其他外，有助于理解肝癌的分子机制，了解导致化学耐药性或预后不良的遗传改变，以及鉴定和评估针对肝细胞癌的新疗法。本发明的肝癌模型通过改变肝细胞以增加癌基因表达，减少肿瘤抑制基因表达或两者并通过将所得肝细胞移植到受体非人动物中来制备。

10. 发明申请

WO2004074445A3 Model for studying the role of genes in tumor resistance to chemotherapy 审中-公开
标题翻译：研究基因在肿瘤抗化疗中的作用模型
公开(公告)号：WO2004074445A3
公开(公告)日：2006-05-18
申请号：PCT/US2004004686
申请日：2004-02-17
申请人： COLD SPRING HARBOR LAB , UNIV MCGILL , FRIDMAN JORDAN S , LOWE SCOTT W , DE STANCHINA ELISA , WENDEL HANS G , PELLETIER JERRY
发明人： FRIDMAN JORDAN S , LOWE SCOTT W , DE STANCHINA ELISA , WENDEL HANS G , PELLETIER JERRY
IPC分类号： A01K67/027 , A61K31/436 , A61P35/00 , C07K14/82 , C12N20060101 , C12N1/00 , C12N5/00 , C12N9/12 , C12N15/12 , C12N15/54 , C12N15/867 , C12Q1/00 , C12Q1/02 , C12Q1/68 , G01N33/50 , A01N43/04 , A01N63/00 , C12N15/00 , C12N15/63
CPC分类号： C12N15/86 , A01K67/0275 , A01K2217/05 , A01K2227/105 , A01K2267/0331 , A01K2267/0393 , C07K14/82 , C12N9/1205 , C12N15/8509 , C12N2740/14043 , G01N33/5011 , G01N33/502 , G01N33/574 , G01N2800/52
摘要： The invention provides the components of in vivo and in vitro systems and methods which use them to study the effects of altered expression of a gene activity, such as the human akt, bcl-2, eIF4E or PTEN activities, on the descendants of stem cells that have been engineered to give rise to hematopoietic tumorigenic or tumor cells, such as lymphomas, with a high frequency. The present invention provides vectors, cells and mammals, and methods which in part depend on such products, useful for understanding tumorigenesis and its treatments, and in particular, for identifying and studying inhibitors and activators associated with tumor cell growth and growth inhibition, cell death through apoptotic pathways, and changes in apoptotic pathway components that affect drug sensitivity and resistance in tumorigenic cells. Methods for identifying molecular targets for drug screening, identifying interacting gene activities, for identifying therapeutic treatments and for identifying candidates for new therapeutic treatments are provided.
摘要翻译：本发明提供体内和体外系统和方法的组分，其使用它们来研究基因活性的表达改变如人类akt，bcl-2，eIF4E或PTEN活性对干细胞后代的影响已被设计成以高频率引起造血致瘤性或肿瘤细胞如淋巴瘤。本发明提供载体，细胞和哺乳动物，以及部分依赖于这些产物的方法，其可用于了解肿瘤发生及其治疗，特别是鉴定和研究与肿瘤细胞生长和生长抑制相关的抑制剂和激活剂，细胞死亡通过细胞凋亡途径以及影响致瘤细胞中药物敏感性和抗性的凋亡途径成分的变化。提供了用于鉴定用于药物筛选的分子靶标，鉴定相互作用的基因活性，用于鉴定治疗性治疗和鉴定新的治疗性治疗候选物的方法。

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