公开(公告)号：WO2019084664A1

公开(公告)日：2019-05-09

申请号：PCT/CA2018/000210

申请日：2018-11-02

Applicant: THE GOVERNORS OF THE UNIVERSITY OF ALBERTA

Inventor： HUBBARD, Basil ,  CROMWELL, Christopher

IPC: C12N15/113 ,  C07K19/00 ,  C12N15/09 ,  C12N15/11 ,  C12N15/63 ,  C12N15/90 ,  C12N9/22

CPC classification number: C12N9/22 ,  C12N15/113 ,  C12N15/62 ,  C12N15/907 ,  C12N2310/20 ,  C12N2310/3125 ,  C12N2310/3231 ,  C12N2310/344 ,  C12N2320/51 ,  C12N2320/53 ,  C12N2310/321 ,  C12N2310/3521 ,  C12N2310/322 ,  C12N2310/3531

Abstract: A method of increasing specificity of binding of a CRISPR-Cas protein-guide RNA complex to a selected target nucleic acid sequence is provided. The method comprises contacting a nucleic acid molecule comprising the selected target nucleic acid sequence with the complex comprising the CRISPR-Cas protein and the guide RNA, wherein the guide RNA comprises a complementarity region at the 5' end of the guide RNA that binds to a complementary strand of the selected target nucleic acid sequence, wherein the guide RNA comprises at least one modified nucleic acid within the complementarity region; wherein the guide RNA complementarity region binds and directs the CRISPR-Cas protein (e.g. CRISPR/Cas9) to the selected target nucleic acid sequence, thereby increasing specificity of binding of the CRISPR-Cas protein-guide RNA complex to the selected target nucleic acid sequence. The modified nucleic acid may be a bridged nucleic acid, a deoxyribonucleic acid, or a 2'-0-methyl RNA phosphonoacetate-modified crRNA, or a functional equivalent that improves specificity by inducing similar conformational changes in the CRISPR-Cas system. Guide RNAs, kits comprising a guide RNA together with a CRISPR-Cas protein, and complexes comprising a guide RNA and a CRISPR-Cas proteins are also provided.

公开(公告)号：WO2017136794A1

公开(公告)日：2017-08-10

申请号：PCT/US2017/016608

申请日：2017-02-03

Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

Inventor： YIN, Hao ,  ANDERSON, Daniel, G. ,  LANGER, Robert, S.

IPC: C12N9/16 ,  C12N9/22 ,  C12N15/113 ,  C07H21/02 ,  C07H21/00 ,  A61K48/00

CPC classification number: C12N15/113 ,  C12N9/16 ,  C12N9/22 ,  C12N15/907 ,  C12N2310/20 ,  C12N2310/315 ,  C12N2310/344 ,  C12N2310/346 ,  C12N2320/32 ,  C12N2310/322 ,  C12N2310/3533 ,  C12N2310/321 ,  C12N2310/3521

Abstract: The disclosure relates to compositions comprising and methods for chemical modification of single guide RNA (sgRNA), tracrRNA and/or crRNA used individually or in combination with one another or Cas system components. Compositions comprising modified ribonucleic acids have been designed with chemical modification for even higher efficiency as unmodified native strand of sgRNA. Administration of modified ribonucleic acids will allow decreased immune response when administered to a subject, increased stability, increased editing efficiency and facilitated in vivo delivery of sgRNA via various delivery platforms. The disclosure also relates to methods of decreasing off-target effect of CRISPR and a CRISPR complex.

Abstract translation: 本公开涉及组合物，所述组合物包含单独或彼此组合使用的单引导RNA（sgRNA），tracrRNA和/或crRNA或Cas系统组分的化学修饰。 包含修饰的核糖核酸的组合物已经被设计成具有与未经修饰的sgRNA天然链更高效的化学修饰。 施用修饰的核糖核酸将允许在施用给受试者时降低的免疫应答，增加的稳定性，增加的编辑效率并且促进经由各种递送平台体内递送sgRNA。 本公开还涉及减少CRISPR和CRISPR复合物的脱靶效应的方法。

公开(公告)号：WO2017015175A1

公开(公告)日：2017-01-26

申请号：PCT/US2016/042694

申请日：2016-07-17

Applicant: ARCTURUS THERAPEUTICS, INC.

Inventor： LIMPHONG, Pattraranee ,  TACHIKAWA, Kiyoshi ,  ESAU, Christine ,  CHIVUKULA, Padmanabh

IPC: A61P1/16 ,  C07H21/00

CPC classification number: C12N15/1131 ,  C12N2310/14 ,  C12N2310/323 ,  C12N2310/344

Abstract: This invention encompasses compounds and compositions useful in methods for medical therapy, in general, for inhibiting Hepatitis B virus in a subject. The compounds have a first strand and a second strand, each of the strands being 19-29 monomers in length, the monomers comprising UNA monomers and nucleic acid monomers, and the compounds are targeted to a sequence of an HBV genome.

Abstract translation: 本发明包括可用于药物治疗方法的化合物和组合物，通常用于在受试者中抑制乙型肝炎病毒。 所述化合物具有第一链和第二链，每条链长度为19-29个单体，所述单体包含UNA单体和核酸单体，并且所述化合物靶向HBV基因组的序列。

公开(公告)号：WO2016183009A2

公开(公告)日：2016-11-17

申请号：PCT/US2016/031471

申请日：2016-05-09

Applicant: DICERNA PHARMACEUTICALS, INC.

Inventor： BROWN, Bob, D. ,  DUDEK, Henryk, T.

IPC: A61K48/00 ,  C07H21/02

CPC classification number: C07H21/02 ,  C12N15/113 ,  C12N2310/11 ,  C12N2310/14 ,  C12N2310/344 ,  C12N2310/345 ,  C12N2310/346 ,  C12N2310/533 ,  C12N2310/321 ,  C12N2310/3521

Abstract: This invention relates to compounds, compositions, and methods useful for reducing AT3 target RNA and protein levels via use of dsRNAs, e.g ., Dicer substrate siRNA (DsiRNA) agents.

Abstract translation: 本发明涉及可用于通过使用dsRNA例如Dicer底物siRNA（DsiRNA）试剂降低AT3靶RNA和蛋白质水平的化合物，组合物和方法。

公开(公告)号：WO2016106404A3

公开(公告)日：2016-09-15

申请号：PCT/US2015067559

申请日：2015-12-28

Applicant: NITTO DENKO CORP ,  YING WENBIN

Inventor： YING WENBIN ,  MINOMI KENJIROU ,  MAJETI BHARAT ,  WANG LI ,  LIU JIHUA ,  ADAMI ROGER

IPC: A61K31/52 ,  A61K31/7088 ,  A61K31/7105 ,  A61K31/711 ,  A61K31/713 ,  A61K38/45

CPC classification number: C12N15/113 ,  C07F9/6533 ,  C12N15/1137 ,  C12N2310/14 ,  C12N2310/322 ,  C12N2310/344 ,  C12N2310/3515 ,  C12N2310/531 ,  C12N2320/30 ,  C12N2320/35 ,  C12Q1/02 ,  G01N33/582

Abstract: This invention provides methods and compositions for preventing, treating or ameliorating one or more symptoms of a malignant tumor associated with KRAS mutation in a mammal in need thereof, by identifying a tumor cell in the mammal, the tumor cell comprising at least one of: (i) a mutation of the KRAS gene, and (ii) an aberrant expression level of KRAS protein; and administering to the mammal a therapeutically effective amount of a composition comprising one or more RNAi molecules that are active in reducing expression of GST-π.

Abstract translation: 本发明提供了用于通过鉴定哺乳动物中的肿瘤细胞来预防，治疗或改善有需要的哺乳动物中与KRAS突变相关的恶性肿瘤的一种或多种症状的方法和组合物，所述肿瘤细胞包含以下至少一种： i）KRAS基因的突变，和（ii）KRAS蛋白的异常表达水平; 并且向哺乳动物施用治疗有效量的包含一种或多种对降低GST-π表达有活性的RNAi分子的组合物。

公开(公告)号：WO2016106400A3

公开(公告)日：2016-09-01

申请号：PCT/US2015067553

申请日：2015-12-28

Applicant: NITTO DENKO CORP ,  YING WENBIN

Inventor： YING WENBIN ,  MINOMI KENJIROU ,  HARBORTH JENS ,  TAKAHASHI HIROKAZU ,  TERADA ERIKA ,  ZHANG JUN ,  AHMADIAN MOHAMMAD

IPC: A61K31/713 ,  A61K31/52

CPC classification number: C12N15/113 ,  C07F9/6533 ,  C12N15/1137 ,  C12N2310/14 ,  C12N2310/322 ,  C12N2310/344 ,  C12N2310/3515 ,  C12N2310/531 ,  C12N2320/30 ,  C12N2320/35 ,  C12Q1/02 ,  G01N33/582

Abstract: This invention provides compounds, compositions and methods for modulating the expression of human GST-pi using RNA interference. The RNA interference molecules can be used in methods for preventing or treating diseases such as malignant tumor. Provided are a range of siRNA structures, having one or more of nucleotides being modified or chemically-modified. Advantageous structures include siRNAs with 2'-deoxy nucleotides located in the seed region, as well as other nucleotide modifications

Abstract translation: 本发明提供了使用RNA干扰来调节人GST-π表达的化合物，组合物和方法。 RNA干扰分子可用于预防或治疗诸如恶性肿瘤的疾病的方法中。 提供一系列siRNA结构，其中一个或多个核苷酸被修饰或化学修饰。 有利的结构包括具有位于种子区域中的2'-脱氧核苷酸的siRNA以及其他核苷酸修饰

公开(公告)号：WO2016002753A1

公开(公告)日：2016-01-07

申请号：PCT/JP2015/068778

申请日：2015-06-30

Applicant: 協和発酵キリン株式会社

Inventor： 細江　慎太郎 ,  直井　智幸

IPC: C07D205/04 ,  A61K9/127 ,  A61K31/713 ,  A61K47/22 ,  A61K48/00 ,  A61P1/16 ,  A61P11/00 ,  A61P13/12 ,  A61P43/00 ,  C12N15/113

CPC classification number: A61K47/541 ,  A61K9/1272 ,  A61K31/7105 ,  A61K31/713 ,  C07D205/04 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/344 ,  C12N2320/32 ,  C12N2310/322 ,  C12N2310/3533

Abstract: 　本発明は、　式(I)　[式中、R 1 およびR 2 は、炭素数8～24のアルキル等であり、R 3 は、水素原子、炭素数1～3のアルキル、式(A) (式中、R 4 およびR 5 は、水素原子等であり、n 3 は2～6の整数である)、または式(B) (式中、R 6 およびR 7 は、水素原子等であり、n 4 は1～6の整数である)であり、　n 1 は0～4の整数であり、n 2 は1～4の整数である(但し、n 1 が0であり、n 2 が1である場合を除く)]で表されるカチオン性脂質、ならびに該カチオン性脂質および核酸を含有する組成物等を提供する。

Abstract translation: 本发明提供由式（I）表示的阳离子脂质（式中，R1和R2是C8-24烷基等，R3是氢原子，C1-3烷基，式（A）（在 式中，R 4和R 5为氢原子等，n 3为2-6的整数）或式（B）（式中，R 6和R 7为氢原子等，n 4为1-6的整数 ），n1为0-4的整数，n2为1-4的整数（但是，n1为0，n2为1的情况除外）），以及含有该阳离子脂质和核酸的组合物等。

公开(公告)号：WO2015198024A1

公开(公告)日：2015-12-30

申请号：PCT/GB2015/051812

申请日：2015-06-23

Applicant: ALTERMUNE LIMITED

Inventor： HALL, Bradley ,  HATALA, Paul

IPC: C12N15/115 ,  A61P35/00

CPC classification number: C12N15/115 ,  C12N2310/16 ,  C12N2310/317 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/344 ,  C12N2310/351 ,  C12N2310/3513 ,  C12N2320/51 ,  C12N2310/3533 ,  C12N2310/3521

Abstract: The invention relates to novel aptamers, in particular aptamers which are capable of binding to EGFR. The invention also relates to cancer cell binding complexes comprising said aptamers and the use of said cancer cell binding complexes in the treatment of cancer.

Abstract translation: 本发明涉及新颖的适体，特别是能够结合EGFR的适体。 本发明还涉及包含所述适体的癌细胞结合复合物以及所述癌细胞结合复合物在癌症治疗中的用途。

公开(公告)号：WO2015051135A3

公开(公告)日：2015-09-03

申请号：PCT/US2014058851

申请日：2014-10-02

Applicant: NOVARTIS AG ,  BARYZA JEREMY LEE ,  BLOMMERS MARCEL ,  BORLAND TODD ,  FERNANDEZ CESAR ,  GEBUHR TOM ,  GENO ERIN ,  GOSSERT ALVAR ,  GREENIDGE PAULETTE ,  HUESKEN DIETER ,  HUNZIKER JUERG ,  NATT FRANCOIS JEAN-CHARLES ,  PATNAIK ANUP ,  PATTERSON ANDREW ,  RONDEAU JEAN-MICHEL RENE ,  SOLOMON JONATHAN ,  WEILER JAN ,  ZHU MEICHENG

Inventor： BARYZA JEREMY LEE ,  BLOMMERS MARCEL ,  BORLAND TODD ,  FERNANDEZ CESAR ,  GEBUHR TOM ,  GENO ERIN ,  GOSSERT ALVAR ,  GREENIDGE PAULETTE ,  HUESKEN DIETER ,  HUNZIKER JUERG ,  NATT FRANCOIS JEAN-CHARLES ,  PATNAIK ANUP ,  PATTERSON ANDREW ,  RONDEAU JEAN-MICHEL RENE ,  SOLOMON JONATHAN ,  WEILER JAN ,  ZHU MEICHENG

IPC: C12N15/113 ,  A61K31/713 ,  A61P7/06

CPC classification number: C12N15/113 ,  C12N15/1136 ,  C12N2310/14 ,  C12N2310/321 ,  C12N2310/344 ,  C12N2310/351 ,  C12N2320/51

Abstract: The present disclosure relates to methods of treating Hepcidin-related diseases such as anemia, iron-deficient erythropoiesis, hypoferremia, impaired dietary iron uptake, iron sequestration, anemia of inflammation (AI) (sometimes designated anemia of chronic disease or ACD), atherosclerosis, diabetes, and multiple neurodegenerative disorders such as Alzheimers disease, Parkinsons disease and Friedrichs ataxia, heart failure, chronic kidney disease, cardiorenal-anemia syndrome, infection, blood loss, hemolysis, vitamin B12 or folate deficiency, hyperparathyroidism, hemoglobinopathies and malignancies, cancer, AIDS, surgery, runted growth, and hair loss, using a therapeutically effective amount of a RNAi agent to Hepcidin.

Abstract translation: 本发明涉及治疗铁调素相关疾病例如贫血，铁缺乏性红细胞生成，低铁血症，饮食铁摄取受损，铁螯合，炎症贫血（AI）（有时称为慢性疾病或ACD贫血），动脉粥样硬化， 糖尿病和多种神经退行性疾病如阿尔茨海默病，帕金森病和弗里德里希共济失调，心力衰竭，慢性肾病，心肾综合征，感染，失血，溶血，维生素B12或叶酸缺乏症，甲状旁腺功能亢进症，血红蛋白病和恶性肿瘤， 艾滋病，手术，运行的生长和脱发，使用治疗有效量的RNAi剂对Hepcidin。

公开(公告)号：WO2015035305A1

公开(公告)日：2015-03-12

申请号：PCT/US2014/054561

申请日：2014-09-08

Applicant: SOMALOGIC, INC.

Inventor： JANJIC, Nebojsa ,  DROLET, Daniel W. ,  GELINAS, Amy D. ,  ZHANG, Chi ,  VRKLJAN, Michael

IPC: C12Q1/68

CPC classification number: C12N15/115 ,  C12N2310/16 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/3341 ,  C12N2310/344 ,  C12N2310/346 ,  C12N2320/51 ,  C12N2310/3521

Abstract: Aptamers having improved stability against nucleases that bind PDGF and aptamers that bind VEGF are provided. In addition, aptamer constructs comprising a PDGF aptamer and a VEGF aptamer are provided. Pharmaceutical compositions comprising the aptamers and aptamer constructs are provided, as well as methods of treating conditions using the aptamers and aptamer constructs.

Abstract translation: 提供了对结合PDGF的核酸酶和结合VEGF的适体具有改善的稳定性的适配子。 此外，提供了包含PDGF适体和VEGF适体的适体构建体。 提供了包含适体和适体构建体的药物组合物，以及使用适体和适体构建体治疗病症的方法。