利索-全球专利检索

  1. 登录
  2. 注册

搜索结果

9 条记录 (耗时 0.024 秒)

    MODIFIED RNAI POLYNUCLEOTIDES AND USES THEREOF
    1.
    发明申请
    MODIFIED RNAI POLYNUCLEOTIDES AND USES THEREOF 审中-公开
    改良的RNAi多核苷酸及其用途

    公开(公告)号：WO2009102427A2

    公开(公告)日：2009-08-20

    申请号：PCT/US2009/000852

    申请日：2009-02-11

    申请人： RXI PHARMACEUTICALS CORP. ,  PAVCO, Pamela, A. ,  KAMENS, Joanne ,  WOOLF, Tod, M. ,  SALOMON, William ,  KHVOROVA, Anastasia

    发明人： PAVCO, Pamela, A. ,  KAMENS, Joanne ,  WOOLF, Tod, M. ,  SALOMON, William ,  KHVOROVA, Anastasia

    IPC分类号： C12N15/11 ,  C07H21/02 ,  A61K31/713

    CPC分类号： C12N15/111 ,  C12N15/113 ,  C12N15/1136 ,  C12N15/1137 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/341 ,  C12N2320/51 ,  C12N2320/53 ,  C12N2310/3521

    摘要： The invention relates to improved RNAi constructs and uses thereof. The construct has a double stranded region of 19-49 nucleotides, preferably 25, 26, or 27 nucleotides, and preferably blunt-ended. The construct has selective minimal modifications to confer an optimal balance of biological activity, toxicity, stability, and target gene specificity. For example, the sense strand may be modified (e.g., one or both ends of the sense strand is/are modified by four 2'-O-methyl groups), such that the construct is not cleaved by Dicer or other RNAse III, and the entire length of the antisense strand is loaded into RISC. In addition, the antisense strand may also be modified by 2'-O-methyl group at the 2nd 5'-end nucleotide to greatly reduce off-target silencing. The constructs of the invention largely avoids the interferon response and sequence- independent apoptosis in mammalian cells, exhibits better serum stability, and enhanced target specificity.

    摘要翻译： 本发明涉及改进的RNAi构建体及其用途。 该构建体具有19-49个核苷酸，优选25,26或27个核苷酸的双链区域，并且优选是平端的。 该构建体具有选择性的最小修饰以赋予生物活性，毒性，稳定性和靶基因特异性的最佳平衡。 例如，有义链可以被修饰（例如，有义链的一个或两个末端被四个2'-O-甲基修饰），使得该构建体不被Dicer或其他RNA酶III切割，以及 反义链的整个长度被加载到RISC中。 此外，反义链也可以通过2'-O-甲基在第二个5'-末端核苷酸修饰，以大大减少脱靶沉默。 本发明的构建体大大避免了哺乳动物细胞中的干扰素反应和序列无关的凋亡，表现出更好的血清稳定性和增强的靶特异性。

    RNAI CONSTRUCTS AND USES THEROF
    5.
    发明申请
    RNAI CONSTRUCTS AND USES THEROF 审中-公开
    RNAI构建和使用

    公开(公告)号：WO2010011346A1

    公开(公告)日：2010-01-28

    申请号：PCT/US2009004326

    申请日：2009-07-23

    申请人： RXI PHARMACEUTICALS CORP ,  SAMARSKY DMITRY ,  WOOLF TOD ,  SALOMON WILLIAM ,  KAMENS JOANNE ,  KHVOROVA ANASTASIA ,  PAVCO PAMELA A

    发明人： SAMARSKY DMITRY ,  WOOLF TOD ,  SALOMON WILLIAM ,  KAMENS JOANNE ,  KHVOROVA ANASTASIA ,  PAVCO PAMELA A

    IPC分类号： A61K31/712 ,  A61K31/713 ,  C12N15/11 ,  C12N15/113

    CPC分类号： C12N15/1137 ,  C12N15/111 ,  C12N2310/14 ,  C12N2310/531 ,  C12N2310/533 ,  C12N2320/51

    摘要： The invention relates to improved double-stranded RNAi constructs (sometimes referred to as "solo-rxRNA") and uses thereof. The construct comprises a structure formed in some aspects of the invention by two identical single-stranded polynucleotides, with the structure having two double-stranded stem regions (each having less than 21 base pairs) and a loop or bulge having about 4 to 11 nucleotides on each strand. The construct is resistant to cleavage by Dicer or other Dicer-like RNase III enzymes and is capable of being loaded into a RISC complex to effect RNA interference. In addition, the nucleotides of the present hairpin constructs may be modified to greatly enhance functionality, such as stability and specificity.

    摘要翻译： 本发明涉及改进的双链RNAi构建体（有时称为“solo-rxRNA”）及其用途。 该构建体包含在本发明的一些方面中由两个相同的单链多核苷酸形成的结构，该结构具有两个双链干区（每个具有少于21个碱基对）和具有约4至11个核苷酸的环或凸起 在每条链上。 该构建体对Dicer或其他类似切酶的RNA酶III酶的切割具有抗性，并且能够加载到RISC复合物中以实现RNA干扰。 另外，可以修饰本发明构建体的核苷酸以大大增强功能性，例如稳定性和特异性。

    MODIFIED RNAI POLYNUCLEOTIDES AND USES THEREOF
    9.
    发明申请
    MODIFIED RNAI POLYNUCLEOTIDES AND USES THEREOF 审中-公开
    修饰的RNAi多核苷酸及其用途

    公开(公告)号：WO2009102427A3

    公开(公告)日：2009-12-23

    申请号：PCT/US2009000852

    申请日：2009-02-11

    申请人： RXI PHARMACEUTICALS CORP ,  PAVCO PAMELA A ,  KAMENS JOANNE ,  WOOLF TOD M ,  SALOMON WILLIAM ,  KHVOROVA ANASTASIA

    发明人： PAVCO PAMELA A ,  KAMENS JOANNE ,  WOOLF TOD M ,  SALOMON WILLIAM ,  KHVOROVA ANASTASIA

    IPC分类号： A61K31/713 ,  C07H21/02 ,  C12N15/113

    CPC分类号： C12N15/111 ,  C12N15/113 ,  C12N15/1136 ,  C12N15/1137 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/341 ,  C12N2320/51 ,  C12N2320/53 ,  C12N2310/3521

    摘要： The invention relates to improved RNAi constructs and uses thereof. The construct has a double stranded region of 19-49 nucleotides, preferably 25, 26, or 27 nucleotides, and preferably blunt-ended. The construct has selective minimal modifications to confer an optimal balance of biological activity, toxicity, stability, and target gene specificity. For example, the sense strand may be modified (e.g., one or both ends of the sense strand is/are modified by four 2'-O-methyl groups), such that the construct is not cleaved by Dicer or other RNAse III, and the entire length of the antisense strand is loaded into RISC. In addition, the antisense strand may also be modified by 2'-O-methyl group at the 2nd 5'-end nucleotide to greatly reduce off-target silencing. The constructs of the invention largely avoids the interferon response and sequence- independent apoptosis in mammalian cells, exhibits better serum stability, and enhanced target specificity.

    摘要翻译： 本发明涉及改进的RNAi构建体及其用途。 构建体具有19-49个核苷酸的双链区，优选25,26或27个核苷酸，并且优选平末端。 该构建体具有选择性最小修饰以赋予生物活性，毒性，稳定性和靶基因特异性的最佳平衡。 例如，有义链可以被修饰（例如，有义链的一个或两个末端被4个2'-O-甲基修饰），使得构建体不被切酶或其他RNA酶III切割，以及 反义链的整个长度被加载到RISC中。 另外，反义链也可以通过第2个5'-末端核苷酸上的2'-O-甲基修饰，以大大减少脱靶沉默。 本发明的构建体在很大程度上避免了哺乳动物细胞中的干扰素应答和序列非依赖性细胞凋亡，表现出更好的血清稳定性和增强的靶特异性。