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.
Type:
Grant
Filed:
March 4, 2016
Date of Patent:
December 19, 2017
Assignees:
Ionis Pharmaceuticals, Inc., Cold Spring Harbor Laboratory
Inventors:
Xue-hai Liang, Stanley T. Crooke, C. Frank Bennett, David L. Spector
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.
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.
Abstract: Methods and compositions for modulating shoot apical meristem size are provided. Methods are provided for modulating the expression of fea3 sequence in a host plant or plant cell to modulate agronomic characteristics such as altered size and number of organs, including plant seeds.
Type:
Application
Filed:
June 2, 2017
Publication date:
September 28, 2017
Applicants:
E I Du Pont De Nemours and Company, Cold Spring Harbor Laboratory
Inventors:
Stephen M. Allen, David Peter Jackson, Byoung IL Je, Mai Komatsu, Young Koung Lee, Hajime Sakai
Abstract: The present invention provides a method of identifying mRNA transcripts in the transcriptome of a cell comprising i) delivering into the cell a donor expression vector comprising nucleotides in a sequence encoding a trans-splicing barcode cassette, ii) exposing the cell to conditions such that the cell produces multiple copies of the trans-splicing barcode cassette encoded by the donor expression vector, which multiple copies of the trans-splicing barcode cassette each splice the barcode polynucleotide onto a mRNA transcript of the cell, thereby forming multiple mRNA transcripts of the cell, each spliced to the barcode polynucleotide; and iii) identifying the multiple mRNA transcripts that are spliced to the barcode polynucleotides, thereby identifying mRNA transcripts in the transcriptome of the cell.
Type:
Grant
Filed:
March 13, 2014
Date of Patent:
September 5, 2017
Assignee:
COLD SPRING HARBOR LABORATORY
Inventors:
Anthony M. Zador, Ian D. Peikon, Petr Znamenskiy
Abstract: Provided herein are genetically-altered Solanaceae plants, compositions related to the Solanaceae plants, and methods of making the Solanaceae plants.
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.
Type:
Grant
Filed:
February 9, 2015
Date of Patent:
August 1, 2017
Assignees:
Biogen MA Inc., Cold Spring Harbor Laboratory
Inventors:
C. Frank Bennett, Gene Hung, Frank Rigo, Adrian R. Krainer, Yimin Hua, Marco A. Passini, Lamya Shihabuddin, Seng H. Cheng, Katherine W. Klinger
Abstract: Methods and compositions for modulating shoot apical meristem size are provided. Methods are provided for modulating the expression of fea3 sequence in a host plant or plant cell to modulate agronomic characteristics such as altered size and number of organs, including plant seeds.
Type:
Grant
Filed:
March 13, 2013
Date of Patent:
July 11, 2017
Assignee:
E I DU PONT DE NEMOURS AND COMPANY COLD SPRING HARBOR LABORATORY
Inventors:
Stephen M Allen, David Peter Jackson, Byoung Il Je, Mai Komatsu, Young Koung Lee, Hajime Sakai
Abstract: The invention relates to the fields of therapeutics and identifying candidates for therapy, in particular to a method of identifying candidates for trastuzumab (Herceptin®) therapy in a patient presenting with breast cancer based on the presence or absence of specific genetic markers in a tumor sample from said patient.
Abstract: The present disclosure relates to compositions and methods for inhibiting nonsense-mediated mRNA decay in a gene-specific manner, for example in the treatment of diseases or disorders caused by nonsense mutations.
Type:
Application
Filed:
September 4, 2014
Publication date:
June 8, 2017
Applicant:
Cold Spring Harbor Laboratory
Inventors:
Adrian Krainer, Isabel Aznarez, Tomoki Nomakuchi
Abstract: The present invention, SMASH (Short Multiply Aggregated Sequence Homologies), is a technique designed to pack multiple independent mappings into every read. Specifically, the invention relates to a composition comprising a first mixture of different chimeric genomic nucleic acid fragments, wherein each different fragment in the mixture comprises randomly ligated DNA segments, wherein each DNA segment in the fragment is a nucleic acid molecule at least 27 base pairs in length resulting from random fragmentation of a single genome. The invention also relates to methods for generating said composition and use of said composition to obtain genomic information, for example, copy number variation.
Type:
Application
Filed:
January 30, 2017
Publication date:
June 1, 2017
Applicant:
Cold Spring Harbor Laboratory
Inventors:
Michael H. Wigler, Dan Levy, Zihua Wang
Abstract: The present invention provides methods of treating cognitive deficits associated with mental retardation. The methods comprise combining cognitive training protocols and a general administration of phosphodiesterase 4 inhibitors.
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.
Type:
Application
Filed:
September 7, 2016
Publication date:
May 4, 2017
Applicant:
Cold Spring Harbor Laboratory
Inventors:
Joshua Dubnau, Wanhe Li, Lisa Prazak, Molly Hammell, Ying Jin
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: 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.
Type:
Application
Filed:
September 16, 2016
Publication date:
March 30, 2017
Applicants:
Biogen MA Inc., Cold Spring Harbor Laboratory
Inventors:
Brenda F. Baker, Adrian R. Krainer, Yimin Hua
Abstract: The present invention relates to transposon activation and mobilization, particularly in the brain, during normal aging; reporter systems to detect such mobilization, along with cells and transgenic animals containing such systems; methods of monitoring neuronal function during normal aging; methods of determining the risk of age-related neuronal decline and age-related mortality; and the use of transposon inhibitors and apoptosis inhibitors to delay age-related neuronal decline and age-related mortality.
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.
Type:
Application
Filed:
February 9, 2015
Publication date:
January 19, 2017
Applicants:
Ionis Pharmaceuticals, Inc., Cold Spring Harbor Laboratory
Inventors:
C. Frank Bennett, Gene Hung, Frank Rigo, Adrian R. Krainer, Yimin Hua, Marco A. Passini, Lamya Shihabuddin, Seng H. Cheng, Katherine W. Klinger
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.
Type:
Grant
Filed:
September 5, 2013
Date of Patent:
September 13, 2016
Assignee:
Cold Spring Harbor Laboratory, LLC
Inventors:
Josh Dubnau, Wanhe Li, Lisa Prazak, Molly Hammell, Ying Jin
Abstract: A method for obtaining from genomic material genomic copy number information unaffected by amplification distortion, comprising obtaining segments of the genomic material, tagging the segments with substantially unique tags to generate tagged nucleic acid molecules, such that each tagged nucleic acid molecule comprises one segment of the genomic material and a tag, subjecting the tagged nucleic acid molecules to amplification by polymerase chain reaction (PCR), generating tag associated sequence reads by sequencing the product of the PCR reaction, assigning each tagged nucleic acid molecule to a location on a genome associated with the genomic material by mapping the subsequence of each tag associated sequence read corresponding to a segment of the genomic material to a location on the genome, and counting the number of tagged nucleic acid molecules having a different tag that have been assigned to the same location on the genome, thereby obtaining genomic copy number information unaffected by amplification d
Type:
Application
Filed:
March 7, 2016
Publication date:
September 1, 2016
Applicant:
Cold Spring Harbor Laboratory
Inventors:
James Hicks, Nicholas Navin, Jennifer Troge, Zihua Wang, Michael Wigler