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    OLIGOMERS WITH IMPROVED OFF-TARGET PROFILE
    6.
    发明申请
    OLIGOMERS WITH IMPROVED OFF-TARGET PROFILE 审中-公开
    具有改进的非目标配置文件的OLIGOMERS

    公开(公告)号：WO2014048441A1

    公开(公告)日：2014-04-03

    申请号：PCT/DK2013/050308

    申请日：2013-09-26

    申请人： MIRRX THERAPEUTICS

    发明人： MOELLER, Thorleif

    IPC分类号： C12N15/113 ,  C07H21/00

    CPC分类号： C12N15/1131 ,  C12N15/111 ,  C12N15/113 ,  C12N2310/11 ,  C12N2310/113 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/3231 ,  C12N2310/341 ,  C12N2320/53 ,  C12N2310/3521

    摘要： The present invention provides oligomers that binds RNA that consists of a lower affinity region and a higher affinity region, wherein the monomers in the higher affinity region increases the melting temperature (i.e. affinity) of the oligomer base paired to RNA more than the monomers used in the lower affinity region, wherein said increase in melting temperature is relatively to the alternative use of DNA monomers of the same (base) sequence. The oligomers of the invention are useful for binding to target RNA such as mRNA and non-coding RNA and have the advantage that they will be less prone to off-target binding via the lower affinity region than via the higher affinity region.

    摘要翻译： 本发明提供了结合由较低亲和力区域和较高亲和力区域组成的RNA的低聚物，其中较高亲和力区域中的单体将与RNA配对的寡聚物碱基的融合温度（即亲和力） 较低的亲和力区域，其中所述升高的熔解温度相对于相同（碱基）序列的DNA单体的替代使用。 本发明的寡聚体可用于结合目标RNA如mRNA和非编码RNA，并且具有的优点是它们通过较低亲合力区域比通过较高亲和力区域更不易于脱靶结合。

    METHODS OF PROMOTING IMMUNE TOLERANCE
    7.
    发明申请
    METHODS OF PROMOTING IMMUNE TOLERANCE 审中-公开
    促进免疫耐受的方法

    公开(公告)号：WO2013040552A3

    公开(公告)日：2013-05-10

    申请号：PCT/US2012055750

    申请日：2012-09-17

    申请人： GEORGIA HEALTH SCIENCES UNIVERSITY

    发明人： MELLOR ANDREW L ,  MUNN DAVID H ,  HUANG LEI ,  SHARMA MADHAV

    IPC分类号： C12N15/117 ,  A61K31/713 ,  C12N15/11

    CPC分类号： A61K47/34 ,  A61K39/02 ,  A61K2039/52 ,  A61K2039/55511 ,  C12N15/111 ,  C12N15/117 ,  C12N2310/17 ,  C12N2320/53

    摘要： Compositions including a polynucleotide combined with a vehicle and methods of their use to induce a suppressive immune response are provided. In some embodiments the compositions induce an increase in expression of indoleamine 2,3 dioxygenase (IDO) enzyme activity in cells. The methods and compositions can be used to inhibit or reduce immune- mediated tissue destruction, to treat autoimmune diseases and inflammatory responses, to promote immune tolerance, to enhance tolerizing vaccines, to treat allergies, to treat asthma, or to enhance mucosal tolerance in subject. Methods and compositions for inducing a suppressive immune response for while minimizing undesirable side effects in the subject are also provided. An exemplary undesirable side effect is systemic release of INFgamma. Exemplary compositions that can be used to induce an immune response in a subject without inducing systemic release of INFgamma include compositions containing a polynucleotide lacking an immunostimulatory nucleic acid sequence complexed with a carrier.

    摘要翻译： 提供了包含与载体组合的多核苷酸的组合物及其用于诱导抑制性免疫应答的方法。 在一些实施方案中，组合物诱导细胞中吲哚胺2,3双加氧酶（IDO）酶活性表达的增加。 所述方法和组合物可用于抑制或减少免疫介导的组织破坏，治疗自身免疫疾病和炎症反应，促进免疫耐受，增强耐受疫苗，治疗变态反应，治疗哮喘或增强对象的粘膜耐受性 。 还提供了用于诱导抑制性免疫应答同时使受试者中不希望的副作用最小化的方法和组合物。 示例性的不良副作用是INFγ的全身释放。 可用于在受试者中诱导免疫应答而不诱导INFγ全身释放的示例性组合物包括含有缺乏与载体复合的免疫刺激性核酸序列的多核苷酸的组合物。

    NUCLEIC ACID MOLECULES AND USES THEREOF
    8.
    发明申请
    NUCLEIC ACID MOLECULES AND USES THEREOF 审中-公开
    核酸分子及其用途

    公开(公告)号：WO2011031561A3

    公开(公告)日：2011-07-07

    申请号：PCT/US2010047026

    申请日：2010-08-27

    申请人： ENSISHEIM PARTNERS LLC ,  QUAY STEVEN C

    发明人： QUAY STEVEN C

    IPC分类号： A61K31/7105 ,  A61K9/20 ,  A61K9/22 ,  A61K38/16 ,  A61K38/17 ,  A61P35/00

    CPC分类号： A61K31/713 ,  A61K9/0019 ,  A61K31/7105 ,  C12N15/111 ,  C12N2310/14 ,  C12N2310/3231 ,  C12N2320/52 ,  C12N2320/53

    摘要： Provided in this application are formulations of double stranded RNA molecules and Krebs Cycle analogs that improving ribonuclease stability, reducing off-target effects of a double stranded siRNA molecule, or of reducing interferon responsiveness of a double stranded siRNA molecule using such dsRNA. Also disclosed are methods of treating a primary tumor or a metastasis by contacting circulating tumor cells, a primary tumor, or a metastasis with a described formulation.

    摘要翻译： 在本申请中提供了双链RNA分子和Krebs Cycle类似物的制剂，其改善了核糖核酸酶稳定性，减少了双链siRNA分子的脱靶效应，或者降低了使用这种dsRNA的双链siRNA分子的干扰素应答性。 还公开了通过使循环肿瘤细胞，原发性肿瘤或转移与所述制剂接触来治疗原发性肿瘤或转移瘤的方法。

    ULTRA-SMALL RNAS AS TOLL-LIKE RECEPTOR-3 ANTAGONISTS
    10.
    发明申请
    ULTRA-SMALL RNAS AS TOLL-LIKE RECEPTOR-3 ANTAGONISTS 审中-公开
    超小RNA作为Toll样受体-3拮抗剂

    公开(公告)号：WO2009105260A3

    公开(公告)日：2009-12-30

    申请号：PCT/US2009001106

    申请日：2009-02-20

    申请人： UNIV KENTUCKY ,  AMBATI JAYAKRISHNA

    发明人： AMBATI JAYAKRISHNA

    IPC分类号： A61K48/00 ,  A61K31/7105 ,  C07H21/02

    CPC分类号： C12N15/8509 ,  A01K67/0276 ,  A01K2217/056 ,  A01K2227/105 ,  A01K2267/0337 ,  A01K2267/0387 ,  C12N15/111 ,  C12N15/117 ,  C12N2310/14 ,  C12N2310/18 ,  C12N2310/3515 ,  C12N2310/53 ,  C12N2320/53

    摘要： Provided are methods and compositions for the treatment or prevention of macular degeneration or other diseases or disorders associated with activation of TLR3. Administration of double-stranded RNAs having a length of 22 nucleotides or less treats or prevents macular degeneration or other diseases or disorders associated with activation of TLR3 due to the ability of the RNAs to bind to but not activate TLR3. Furthermore, all double-stranded RNAs (both targeted and non- targeted) of 22 nucleotides or less in length can bind to but not activate TLR3 and thereby treat or prevent such conditions. Also provided is a method for increasing the specificity of a desired siRNA target knockdown, the method comprising administering an amount of a target siRNA sufficient to knockdown a target gene and an amount of a double stranded RNA of 22 nucleotides or less which prevents the target siRNA from activating TLR3.

    摘要翻译： 提供用于治疗或预防与TLR3活化相关的黄斑变性或其他疾病或病症的方法和组合物。 具有22个核苷酸或更少长度的双链RNA的施用治疗或预防由于RNA结合但不激活TLR3的能力而引起的黄斑变性或与TLR3的激活相关的其他疾病或病症。 此外，长度为22个核苷酸或更少的所有双链RNA（靶向和非靶向二者）都可结合但不激活TLR3，从而治疗或预防此类病症。 还提供了用于提高所需siRNA靶向敲低的特异性的方法，所述方法包括施用足以敲低靶基因的量的靶标siRNA和一定量的22个核苷酸或更少的双链RNA，其阻止靶标siRNA 从激活TLR3。