公开(公告)号：US20190071666A1

公开(公告)日：2019-03-07

申请号：US16091913

申请日：2017-04-05

Applicant: Cold Spring Harbor Laboratory

Inventor： Anthony Zador ,  Justus Kebschull

IPC: C12N15/10 ,  C07K14/18 ,  C12N5/0793 ,  C40B70/00

Abstract: The present invention provides a composition comprising a plurality of labeled neurons, each of which is labeled by an expression construct that encodes a unique barcoded nucleic acid.

公开(公告)号：US20190030058A1

公开(公告)日：2019-01-31

申请号：US15892560

申请日：2018-02-09

Applicant: Biogen MA Inc. ,  Cold Spring Harbor Laboratory

Inventor： C. Frank Bennett ,  Gene Hung ,  Frank Rigo ,  Adrian R. Krainer ,  Yimin Hua ,  Marco A. Passini ,  Lamya Shihabuddin ,  Seng H. Cheng ,  Katherine W. Klinger

IPC: A61K31/7088 ,  C12N15/113 ,  A61K31/712

Abstract: Disclosed herein are compounds, compositions and methods for modulating splicing of SMN2 mRNA in a subject. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders, including spinal muscular atrophy.

公开(公告)号：US20180023139A1

公开(公告)日：2018-01-25

申请号：US15546106

申请日：2016-01-26

Applicant: Cold Spring Harbor Laboratory

Inventor： Christopher H. Vakoc ,  Junwei Shi ,  Justin B. Kinney

IPC: C12Q1/68 ,  G01N33/68

CPC classification number: C12Q1/6876 ,  C12N9/22 ,  C12N15/102 ,  C12N15/111 ,  C12N15/63 ,  C12N2310/10 ,  C12N2310/20 ,  C12N2320/12 ,  C12N2330/31 ,  C12Q1/6897 ,  C12Q2600/156 ,  C12Q2600/178 ,  G01N33/68 ,  G01N33/6803

Abstract: Provided herein, in some aspects, are methods of determining whether a candidate protein, more specifically a functional domain of a candidate protein, is essential for viability of cells of interest using clustered regularly interspaced short palindromic repeat (CPJSPR)-Cas9 technology which holds great promise for genetic screening and for the discovery of therapeutic targets.

公开(公告)号：US20170342410A1

公开(公告)日：2017-11-30

申请号：US15451016

申请日：2017-03-06

Applicant: Gregory J. Hannon ,  Sihem Cheloufi

Inventor： Gregory J. Hannon ,  Sihem Cheloufi

IPC: C12N15/113 ,  C12N15/11

CPC classification number: C12N15/113 ,  A01K2207/05 ,  C12N15/111 ,  C12N2310/14 ,  C12N2310/141 ,  C12N2310/531 ,  C12N2320/30

Abstract: Provided is an improved design of shRNA based on structural mimics of miR-451 precursors. These miR-451 shRNA mimics are channeled through a novel small RNA biogenesis pathway, require AGO2 catalysis and are processed by Drosha but are independent of DICER processing. This miRNA pathway feeds active elements only into Agog because of its unique catalytic activity. These data demonstrate that this newly identified small RNA biogenesis pathway can be exploited in vivo to produce active molecules.

公开(公告)号：US20170306392A1

公开(公告)日：2017-10-26

申请号：US15515913

申请日：2015-10-09

Applicant: Cold Spring Harbor Laboratory

Inventor： Michael Wigler ,  Dan Levy

IPC: C12Q1/68 ,  C07H21/04 ,  C12N15/10

CPC classification number: C12Q1/6827 ,  C07H21/04 ,  C12N15/102 ,  C12N15/1031 ,  C12N15/1058 ,  C12Q1/6851 ,  C12Q1/6869 ,  C12Q2521/539 ,  C12Q2525/161 ,  C12Q2531/113 ,  C12Q2535/122 ,  C12Q2545/114

Abstract: A method for determining the number of nucleic acid molecules (NAMs) in a group of NAMs, comprising i) obtaining an amplified and mutagenized group of NAMs that was produced by a. subjecting the group of NAMs to a chemical mutagenesis which mutates only select nucleic acid bases in the group of NAMs at a rate of 10% to 90% thus forming a group of mutagenized NAMs (mNAMs), and b. amplifying the group of mNAMs; ii) obtaining sequences of the mNAMs in the group of amplified mNAMs; and iii) counting the number of different sequences obtained in step (ii) to determine the number of unique mNAMs in the group of mNAMS, thereby determining the number of NAMs in the group of NAMs.

公开(公告)号：US09441223B2

公开(公告)日：2016-09-13

申请号：US14019380

申请日：2013-09-05

Applicant: Cold Spring Harbor Laboratory

Inventor： Josh Dubnau ,  Wanhe Li ,  Lisa Prazak ,  Molly Hammell ,  Ying Jin

IPC: A61K48/00 ,  C07H21/02 ,  C07H21/04 ,  C12N15/113 ,  C12Q1/68

CPC classification number: C12Q1/6883 ,  C12N15/113 ,  C12N15/1137 ,  C12N2310/141 ,  C12Q2600/106 ,  C12Q2600/158

Abstract: A method that includes measuring the expression level of at least one transposon in a biological sample from a subject; and determining whether the measured transposon expression exceeds a predetermined level, and if so, administering to the subject a transposon inhibitor in an amount effective to reduce the expression level of a transposon.

Abstract translation: 一种方法，其包括测量来自受试者的生物样品中至少一个转座子的表达水平; 以及确定所测量的转座子表达是否超过预定水平，如果是，则以有效降低转座子表达水平的量向对象施用转座子抑制剂。

公开(公告)号：US20160194637A1

公开(公告)日：2016-07-07

申请号：US15061843

申请日：2016-03-04

Applicant: Ionis Pharmaceuticals, Inc. ,  Cold Spring Harbor Laobratory

Inventor： Xue-hai Liang ,  Stanley T. Crooke ,  C. Frank Bennett ,  David L. Spector

IPC: C12N15/113

CPC classification number: C12N15/113 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/3231 ,  C12N2310/341 ,  C12N2310/351 ,  C12N2310/3521 ,  C12N2310/3525 ,  C12N2310/3533 ,  C12N2320/30

Abstract: The present invention provides compounds and methods for modulating target nucleic acids found in organelles or sub-organelles of cells. The invention includes, but is not limited to compounds and methods that modulate target nucleic acids in a sub-nuclear organelle, such as the nucleolus and/or a cajal body. In certain embodiments, the cell is in an animal.

公开(公告)号：US20150353929A1

公开(公告)日：2015-12-10

申请号：US14584112

申请日：2014-12-29

Applicant: Isis Pharmaceuticals, Inc. ,  Cold Spring Harbor Laboratory

Inventor： Brenda F. Baker ,  Adrian R. Krainer ,  Yimin Hua

IPC: C12N15/113

CPC classification number: C12N15/113 ,  C12N15/111 ,  C12N2310/11 ,  C12N2310/321 ,  C12N2310/3341 ,  C12N2320/33 ,  C12N2310/3525

Abstract: Disclosed herein are compounds, compositions and methods for modulating splicing of SMN2 mRNA in a cell, tissue or animal. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders, including spinal muscular atrophy.

Abstract translation: 本文公开了用于调节细胞，组织或动物中SMN2mRNA的剪接的化合物，组合物和方法。 还提供了所公开的化合物和组合物在制备用于治疗疾病和病症（包括脊髓性肌肉萎缩）的药物中的用途。

公开(公告)号：US20150197749A1

公开(公告)日：2015-07-16

申请号：US14630419

申请日：2015-02-24

Applicant: Gregory J. Hannon ,  Sihem Cheloufi

Inventor： Gregory J. Hannon ,  Sihem Cheloufi

IPC: C12N15/113

CPC classification number: C12N15/113 ,  A01K2207/05 ,  C12N15/111 ,  C12N2310/14 ,  C12N2310/141 ,  C12N2310/531 ,  C12N2320/30

Abstract: Provided is an improved design of shRNA based on structural mimics of miR-451 precursors. These miR-451 shRNA mimics are channeled through a novel small RNA biogenesis pathway, require AGO2 catalysis and are processed by Drosha but are independent of DICER processing. This miRNA pathway feeds active elements only into Ago2 because of its unique catalytic activity. These data demonstrate that this newly identified small RNA biogenesis pathway can be exploited in vivo to produce active molecules.

Abstract translation: 提供了基于miR-451前体结构模拟的shRNA的改进设计。 这些miR-451 shRNA模拟物通过新的小RNA生物发生途径引导，需要AGO2催化，并且由Drosha处理，但是独立于DICER处理。 由于其独特的催化活性，该miRNA通路将活性成分仅供应到Ago2中。 这些数据表明，这种新鉴定的小RNA生物发生途径可以在体内被利用来产生活性分子。

公开(公告)号：US20150025231A1

公开(公告)日：2015-01-22

申请号：US14371941

申请日：2013-01-11

Applicant: Isis Pharmaceuticals, Inc. ,  Cold Spring Harbor Laboratory

Inventor： C. Frank Bennett ,  Frank Rigo ,  Adrian R. Krainer ,  Rahul Sinha

IPC: C12N15/113

CPC classification number: C12N15/113 ,  C12N15/111 ,  C12N2310/11 ,  C12N2310/113 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/3233 ,  C12N2310/3521 ,  C12N2310/3525 ,  C12N2310/3533 ,  C12N2320/33

Abstract: The present disclosure provides compounds comprising oligonucleotides complementary to a portion of the IKBKAP gene. Certain such compounds are useful for hybridizing to a portion of the IKBKAP gene, including but not limited to a portion of the IKBKAP gene in a cell. In certain embodiments, such hybridization results in modulation of splicing of the IKBKAP gene. In certain embodiments, the IKBKAP gene includes a mutation that results in defective splicing and a truncated IKAP protein. In certain embodiments, hybridization of oligonucleotides complementary to a portion of the IKBKAP gene results in a decrease in the amount of defective splicing and truncated IKAP protein. In certain embodiments, hybridization of oligonucleotides complementary to a portion of the IKBKAP gene results in an increase in the amount of normal splicing and functional, full-length IKAP protein. In certain embodiments, oligonucleotides are used to treat Familial Dysautonomia.

Abstract translation: 本公开提供了包含与IKBKAP基因的一部分互补的寡核苷酸的化合物。 某些这样的化合物可用于与IKBKAP基因的一部分杂交，包括但不限于细胞中IKBKAP基因的一部分。 在某些实施方案中，这种杂交导致IKBKAP基因剪接的调节。 在某些实施方案中，IKBKAP基因包括导致有缺陷的剪接和截短的IKAP蛋白的突变。 在某些实施方案中，与IKBKAP基因的一部分互补的寡核苷酸的杂交导致有缺陷的剪接和截短的IKAP蛋白的量的减少。 在某些实施方案中，与IKBKAP基因的一部分互补的寡核苷酸的杂交导致正常剪接和功能性全长IKAP蛋白的量的增加。 在某些实施方案中，寡核苷酸用于治疗家族性生理压力。