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:
May 3, 2019
Publication date:
November 28, 2019
Applicant:
Cold Spring Harbor Laboratory
Inventors:
Michael H. Wigler, Dan Levy, Zihua Wang
Abstract: Provided herein are methods, compounds, and compositions for reducing expression of Inc05 in a cell or individual. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate a cancer in an individual.
Type:
Application
Filed:
December 1, 2017
Publication date:
November 14, 2019
Applicants:
Cold Spring Harbor Laboratory, Ionis Pharmaceuticals, Inc.
Inventors:
Allen Tingjin Yu, David L. Spector, Frank Rigo, Susan M. Freier, Jan Bermann, Carmen Berasain
Abstract: The present invention provides compounds comprising oligonucleotides complementary to a pyruvate kinase M transcript. Certain such compounds are useful for hybridizing to a pyruvate kinase M transcript, including but not limited to a pyruvate kinase M transcript in a cell. In certain embodiments, such hybridization results in modulation of splicing of the pyruvate kinase M transcript. In certain embodiments, such compounds are used to treat one or more symptoms associated with cancer.
Type:
Application
Filed:
October 2, 2018
Publication date:
August 15, 2019
Applicants:
Ionis Pharmaceuticals, Inc., Cold Spring Harbor Laboratory
Inventors:
Frank Rigo, C. Frank Bennett, Adrian R. Krainer, Zhenxun Wang
Abstract: The present disclosure provides methods for increasing meiotic recombination in crop plants, as well as plants and seeds produced by such methods.
Type:
Application
Filed:
June 29, 2017
Publication date:
August 8, 2019
Applicants:
Cold Spring Harbor Laboratory, Cambridge Enterprise Limited
Inventors:
Rob Martienssen, Charles Underwood, Ian Henderson
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.
Type:
Grant
Filed:
May 30, 2018
Date of Patent:
July 9, 2019
Assignees:
IONIS PHARMACEUTICALS, INC., COLD SPRING HARBOR LABORATORY
Inventors:
C. Frank Bennett, Frank Rigo, Adrian R. Krainer, Rahul Sinha
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 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 polymerase chain reaction (PCR) amplification, 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 assigned to the same location on the genome having a different tag, thereby obtaining genomic copy number information unaffected by amplification distortion.
Type:
Application
Filed:
February 7, 2019
Publication date:
May 23, 2019
Applicant:
Cold Spring Harbor Laboratory
Inventors:
James Hicks, Nicholas Navin, Jennifer Troge, Zihua Wang, Michael Wigler
Abstract: Genetically altered sorghum plants expressing the multi-seeded #2 phenotype contain one of two genomic alterations in the Sb06g018040 gene which result in reduced activity of the encoded protein, a class II 13-lipoxygenase. This phenotype and genotype are referred to as msd2. These alterations result in increased number of seeds and seed weight, thus increasing the yield of the genetically altered plant. These alterations can be generated in the ortholog genes in maize (TS1), rice, barley, and other monocot plants, generating the MSD2 phenotype. The seeds of one particular MSD2 Sorghum bicolor has been deposited with ATCC and assigned Accession Number PTA-121634.
Type:
Grant
Filed:
March 31, 2016
Date of Patent:
April 9, 2019
Assignees:
The United States of America, as represented by the Secretary of Agriculture, Cold Spring Harbor Laboratory
Inventors:
Zhanguo Xin, Gloria B. Burow, Chad M Hayes, John J. Burke, Doreen Ware, Yinping Jiao
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.
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, 2018
Publication date:
January 31, 2019
Applicants:
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: 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: 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.
Type:
Application
Filed:
May 30, 2018
Publication date:
December 27, 2018
Applicants:
Ionis Pharmaceuticals, Inc., Cold Spring Harbor Laboratory
Inventors:
C. Frank Bennett, Frank Rigo, Adrian R. Krainer, Rahul Sinha
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:
November 20, 2017
Publication date:
October 11, 2018
Applicants:
Biogen MA Inc., Cold Spring Harbor Laboratory
Inventors:
Brenda F. Baker, Adrian R. Krainer, Yimin Hua
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.
Type:
Application
Filed:
January 26, 2016
Publication date:
January 25, 2018
Applicant:
Cold Spring Harbor Laboratory
Inventors:
Christopher H. Vakoc, Junwei Shi, Justin B. Kinney
Abstract: Methods and compositions for modulating shoot apical meristem size are provided. Methods are provided for modulating the expression of Fea4 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 14, 2013
Date of Patent:
December 26, 2017
Assignees:
E. I. du Pont de Nemours And Company, Cold Spring Harbor Laboratory, Iowa State University Research Foundation, Inc.
Inventors:
Stephen M Allen, David Peter Jackson, Mai Komatsu, Michael Pautler, Hajime Sakai, Erik Vollbrecht, Rebecca Weeks