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1. 发明专利

CA2561868C MODIFIED POLYNUCLEOTIDES FOR REDUCING OFF-TARGET EFFECTS IN RNA INTERFERENCE 未知
公开(公告)号：CA2561868C
公开(公告)日：2012-11-06
申请号：CA2561868
申请日：2005-03-31
申请人： DHARMACON INC , ROSETTA INPHARMATICS LLC
发明人： LEAKE DEVIN , FEDOROV YURIY , REYNOLDS ANGELA , KHVOROVA ANASTASIA , MARSHALL WILLIAM , LINSLEY PETER S
IPC分类号： C12N15/11 , A01H1/00 , A61K31/713 , C07H21/02 , C12N15/113 , C12N15/82
摘要： Methods and compositions for performing RNA interference with decreased off-target effects are provided. The methods and compositions permit effective and efficient applications of RNA interference to applications such as diagnostics and therapeutics through the use of modifications to the siRNA. Uniquely modified siRNAs have been developed that reduce off-target effects incurred in gene-silencing. The modifications comprise 2'-O-alkyl or mismatch modification(s) at specific positions on the sense and/or antisense strands.

2. 发明专利

JP2010172344A Modified polynucleotide for use in rna interference 有权
标题翻译：用于RNA干扰的改性多核苷酸
公开(公告)号：JP2010172344A
公开(公告)日：2010-08-12
申请号：JP2010106021
申请日：2010-04-30
申请人： Dharmacon Inc , ダーマコン, インコーポレイテッド
发明人： LEAKE DEVIN , REYNOLDS ANGELA , KHVOROVA ANGELA , MARSHALL WILLIAM , FEDOROV YURIY , NICHOLS KIMBERLY
IPC分类号： C12N15/113 , A61K31/713 , A61P35/00
摘要： PROBLEM TO BE SOLVED: To provide a modification for an siRNA capable of increasing or decreasing specificity and/or stability. SOLUTION: There are provided a method and a composition for performing RNA interference comprising a wide variety of stabilized siRNAs suitable for use in serum-containing media and for in vivo applications (such as therapeutic applications). Uniquely modified siRNAs have been developed that reduce off-target effects incurred in gene-silencing. The modifications include phosphorylation of the first 5' terminal antisense nucleotide; 2' carbon modifications of the first and second or first, second and third 5' terminal antisense nucleotides; and optionally 2' carbon modifications of the first and second or first, second and third 5' terminal sense nucleotides. Control and exaequo molecules are also provided. COPYRIGHT: (C)2010,JPO&INPIT
摘要翻译：要解决的问题：提供能够增加或降低特异性和/或稳定性的siRNA的修饰。提供了一种用于进行RNA干扰的方法和组合物，其包含适用于含血清培养基和体内应用（例如治疗应用）的各种稳定的siRNA。已经开发了独特修饰的siRNA，其减少在基因沉默中引起的脱靶效应。修饰包括前5'末端反义核苷酸的磷酸化; 2'碳修饰的第一和第二，第二和第三个5'末端反义核苷酸; 和第一和第二，第二和第三个5'末端有义核苷酸的任选的2'碳修饰。还提供对照和exaequo分子。版权所有（C）2010，JPO＆INPIT

3. 发明专利

AU2005230850B2 Modified polynucleotides for reducing off-target effects in RNA interference 未知
公开(公告)号：AU2005230850B2
公开(公告)日：2009-09-17
申请号：AU2005230850
申请日：2005-03-31
申请人： DHARMACON INC , MERCK & CO INC
发明人： LEAKE DEVIN , FEDOROV YURIY , MARSHALL WILLIAM , REYNOLDS ANGELA , KHVOROVA ANASTASIA
IPC分类号： A01H1/00 , C07H21/02 , C12N15/11 , C12N15/113 , C12N15/82
摘要： Methods and compositions for performing RNA interference with decreased off-target effects are provided. The methods and compositions permit effective and efficient applications of RNA interference to applications such as diagnostics and therapeutics through the use of modifications to the siRNA. Uniquely modified siRNAs have been developed that reduce off-target effects incurred in gene-silencing. The modifications comprise 2′-O-alkyl or mismatch modification(s) at specific positions on the sense and/or antisense strands.

4. 发明专利

AT447024T 未知
公开(公告)号：AT447024T
公开(公告)日：2009-11-15
申请号：AT05712710
申请日：2005-02-04
申请人： DHARMACON INC
发明人： LEAKE DEVIN , KHVOROVA ANASTASIA , FEDOROV YURIY , DELANEY MICHAEL , ROBERTSON BARBARA , ANDERSON EMILY
IPC分类号： A61K31/7088 , A61K38/00 , C12N15/113

5. 发明专利

AT536408T 未知
公开(公告)号：AT536408T
公开(公告)日：2011-12-15
申请号：AT04749718
申请日：2004-04-01
申请人： DHARMACON INC
发明人： LEAKE DEVIN , REYNOLDS ANGELA , KHVOROVA ANASTASIA , MARSHALL WILLIAM , FEDOROV YURIY , NICHOLS KIMBERLY
IPC分类号： C12N15/113 , A61K31/713

6. 发明专利

DE602005017362D1 未知
公开(公告)号：DE602005017362D1
公开(公告)日：2009-12-10
申请号：DE602005017362
申请日：2005-02-04
申请人： DHARMACON INC
发明人： LEAKE DEVIN , KHVOROVA ANASTASIA , FEDOROV YURIY , DELANEY MICHAEL O , ROBERTSON BARBARA , ANDERSON EMILY
IPC分类号： A61K31/7088 , A61K38/00 , C12N15/113

7. 发明专利

CA2561868A1 MODIFIED POLYNUCLEOTIDES FOR REDUCING OFF-TARGET EFFECTS IN RNA INTERFERENCE 未知
公开(公告)号：CA2561868A1
公开(公告)日：2005-10-20
申请号：CA2561868
申请日：2005-03-31
申请人： DHARMACON INC
发明人： FEDOROV YURIY , MARSHALL WILLIAM , REYNOLDS ANGELA , KHVOROVA ANASTASIA , LEAKE DEVIN
IPC分类号： A01H1/00 , A61K31/713 , C07H21/02 , C12N15/11 , C12N15/113 , C12N15/82
摘要： Methods and compositions for performing RNA interference with decreased off- target effects are provided. The methods and compositions permit effective a nd efficient applications of RNA interference to applications such as diagnosti cs and therapeutics through the use of modifications to the siRNA. Uniquely modified siRNAs have been developed that reduce off-target effects incurred in gene-silencing. The modifications comprise 2'-O-alkyl or mismatch modification(s) at specific positions on the sense and/or antisense strands.

8. 发明专利

AU2005230850A1 Modified polynucleotides for reducing off-target effects in RNA interference 未知
公开(公告)号：AU2005230850A1
公开(公告)日：2005-10-20
申请号：AU2005230850
申请日：2005-03-31
申请人： DHARMACON INC
发明人： LEAKE DEVIN , FEDOROV YURIY , MARSHALL WILLIAM , REYNOLDS ANGELA , KHVOROVA ANASTASIA
IPC分类号： A01H1/00 , A61K31/713 , C07H21/02 , C12N15/11 , C12N15/113 , C12N15/82
摘要： Methods and compositions for performing RNA interference with decreased off-target effects are provided. The methods and compositions permit effective and efficient applications of RNA interference to applications such as diagnostics and therapeutics through the use of modifications to the siRNA. Uniquely modified siRNAs have been developed that reduce off-target effects incurred in gene-silencing. The modifications comprise 2′-O-alkyl or mismatch modification(s) at specific positions on the sense and/or antisense strands.

9. 发明申请

WO2005097992A3 MODIFIED POLYNUCLEOTIDES FOR REDUCING OFF-TARGET EFFECTS IN RNA INTERFERENCE 审中-公开
标题翻译：用于减少RNA干扰中的非目标效应的改性多核苷酸
公开(公告)号：WO2005097992A3
公开(公告)日：2006-02-02
申请号：PCT/US2005011008
申请日：2005-03-31
申请人： DHARMACON INC , LEAKE DEVIN , FEDOROV YURIY , REYNOLDS ANGELA , KHVOROVA ANASTASIA , MARSHALL WILLIAM
发明人： LEAKE DEVIN , FEDOROV YURIY , REYNOLDS ANGELA , KHVOROVA ANASTASIA , MARSHALL WILLIAM
IPC分类号： A01H1/00 , C07H21/02 , C12N15/11 , C12N15/113 , C12N15/82 , A61K31/713
CPC分类号： C12N15/111 , C12N15/1137 , C12N15/1138 , C12N2310/14 , C12N2310/315 , C12N2310/321 , C12N2310/322 , C12N2320/11 , C12N2330/30 , C12Y207/11024 , C12Y301/03001 , C12N2310/3521
摘要： Methods and compositions for performing RNA interference with decreased off-target effects are provided. The methods and compositions permit effective and efficient applications of RNA interference to applications such as diagnostics and therapeutics through the use of modifications to the siRNA. Uniquely modified siRNAs have been developed that reduce off-target effects incurred in gene-silencing. The modifications comprise 2'-O-alkyl or mismatch modification(s) at specific positions on the sense and/or antisense strands.
摘要翻译：提供了用于进行RNA干扰减少脱靶效应的方法和组合物。所述方法和组合物允许通过使用对siRNA的修饰来有效和有效地将RNA干扰应用于诸如诊断和治疗的应用。已经开发了独特修饰的siRNA，其减少在基因沉默中引起的脱靶效应。修饰包括在有义和/或反义链上的特定位置上的2'-O-烷基或错配修饰。

10. 发明申请

WO2005090606A2 IDENTIFICATION OF TOXIC NUCLEOTIDE SEQUENCES 审中-公开
标题翻译：鉴定毒素核苷酸序列
公开(公告)号：WO2005090606A2
公开(公告)日：2005-09-29
申请号：PCT/US2005003131
申请日：2005-01-21
申请人： DHARMACON INC
发明人： FEDOROV YURIY , KARPILOW JON , KHVOROVA ANASTASIA
IPC分类号： C07H21/02 , C07H21/04 , C12N15/11 , C12Q1/68 , G01N33/48 , G01N33/50 , G06F19/00
CPC分类号： C12Q1/6883 , C12N15/111 , C12N2310/14 , C12N2310/53 , C12N2320/10 , C12Q2600/142
摘要： Toxic nucleic acid sequences and methods for identifying, using, and screening libraries for them, including in silico screening, are provided. Compositions of the invention comprise unimolecular and double stranded polynucleotides comprising at least one toxicity region. Toxic sequences of the invention include A/G UUU A/G/U, G/C AAA G/C, and/or GCCA, NUUU, wherein N is any nucleotide, or complements thereof. The invention also provides a method of inducing a toxic response in a cell, comprising introducing into the cell a unimolecular or double stranded polynucleotide comprising at least one toxicity region comprising a sequence selected from the group consisting of A/G UUU A/G/U, G/C AAA G/C, GAAT, and GCCA, NUUU, wherein N is any nucleotide, or a complement of any of the foregoing, wherein said unimolecular or double stranded polynucleotide is at least 5 base pairs long and is comprises a sense and antisense region that are at least substantially complementary.
摘要翻译：提供了有毒的核酸序列和用于识别，使用和筛选其文库的方法，包括计算机筛选。本发明的组合物包含包含至少一个毒性区域的单分子和双链多核苷酸。本发明的毒性序列包括A / G UUU A / G / U，G / C AAA G / C和/或GCCA，NUUU，其中N是任何核苷酸或其互补序列。本发明还提供了在细胞中诱导毒性反应的方法，包括向细胞中引入单分子或双链多核苷酸，所述单分子或双链多核苷酸包含至少一个毒性区，其包含选自A / G UUU A / G / U ，G / C AAA G / C，GAAT和GCCA，NUUU，其中N是任何前述的任何核苷酸或补体，其中所述单分子或双链多核苷酸长至少5个碱基对，并且包含感觉和至少基本上互补的反义区。

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