Patents by Inventor Phillip A. Sharp
Phillip A. Sharp has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
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Patent number: 12116619Abstract: The present invention relates to in vivo methods for modeling tumor formation and/or tumor evolution comprising the use of eukaryotic cells in which one or more genetic target locus has been altered by the CRISPR/Cas system, and which cells are transplanted in non-human eukaryote as a model system for tumor formation and tumor evolution. In particular in vivo genetic screening methods for identifying genes involved in tumorigenesis and metastasis are disclosed. The invention further relates to kits and components for practicing the methods, as well as materials obtainable by the methods, in particular tumor and metastasis samples and cells or cell lines derived therefrom. The invention also relates to diagnostic and therapeutic methods derived from the information obtained in the modeling methods.Type: GrantFiled: June 30, 2017Date of Patent: October 15, 2024Assignees: The Broad Institute, Inc., Massachusetts Institute of TechnologyInventors: Sidi Chen, Randall Jeffrey Platt, Neville Espi Sanjana, Phillip A. Sharp, Feng Zhang
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Publication number: 20230265405Abstract: The present disclosure provides a method of editing a genome in a cell including exposing the cell to an engineered Cas nuclease comprising one or more mutations within the DNA binding cleft of the Cas nuclease, wherein exposure to the engineered Cas nuclease decreases, inhibits, or prevents non-homologous end joining (NHEJ) in the cell, and wherein exposure to the engineered Cas nuclease increases one or more homology-driven repair pathways within the cell. The mutant Cas nuclease is also disclosed herein.Type: ApplicationFiled: December 21, 2022Publication date: August 24, 2023Inventors: VIKASH PAL SINGH CHAUHAN, PHILLIP A. SHARP, ROBERT LANGER
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Publication number: 20230121232Abstract: The present disclosure relates to a method of sequencing nascent RNA in a cell. In some embodiments, the nascent RNA is conjugated to DNA using copper-catalyzed azide-alkyne cycloaddition (CuAAC). Methods of the present disclosure can be used to generate genomic libraries of a cell and measure gene expression and enhancer and/or super-enhancer activity.Type: ApplicationFiled: November 2, 2022Publication date: April 20, 2023Applicant: Massachusetts Institute of TechnologyInventors: Phillip A. Sharp, Dig Mahat
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Patent number: 11519027Abstract: The present disclosure relates to a method of sequencing nascent RNA in a cell. In some embodiments, the nascent RNA is conjugated to DNA using copper-catalyzed azide-alkyne cycloaddition (CuAAC). Methods of the present disclosure can be used to generate genomic libraries of a cell and measure gene expression and enhancer and/or super-enhancer activity.Type: GrantFiled: March 29, 2019Date of Patent: December 6, 2022Assignee: Massachusetts Institute of TechnologyInventors: Phillip A. Sharp, Dig Mahat
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Publication number: 20220120736Abstract: Described herein are compositions and methods for modulating gene regulation by modulating condensate formation, composition, maintenance, dissolution and regulation.Type: ApplicationFiled: March 22, 2019Publication date: April 21, 2022Inventors: Richard A. Young, Phillip A. Sharp, Arup K. Chakraborty, Alessandra Dall'Agnese, Krishna Shrinivas, Brian J. Abraham, Ann Boija, Eliot Coffey, Daniel S. Day, Yang E. Guo, Nancy M. Hannett, Tong Ihn Lee, Charles H. Li, Isaac Klein, John C. Manteiga, Benjamin R. Sabari, Jurian Schuijers, Abraham S. Weintraub, Alicia V. Zamudio, Lena K. Afeyan, Ozgur Oksuz, Jonathan E. Henninger
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Patent number: 11124796Abstract: The invention involves inducing 3-50 or more mutations (e.g., any whole number between 3 and 50 of mutations, with it noted that in some embodiments there can be up to 16 different RNA(s), e.g., sgRNAs each having its own a promoter, in a vector, such as AAV, and that when each sgRNA does not have its own promoter, there can be twice to thrice that amount of different RNA(s), e.g., sgRNAs, e.g., 32 or even 48 different guides delivered by one vector) in transgenic Cas9 eukaryotes to model genetic disease, e.g. cancer. The invention comprehends testing putative treatments with such models, e.g., testing putative chemical compounds that may be pharmaceutically relevant for treatment or gene therapy that may be relevant for treatment, or combinations thereof. The invention allows for the study of genetic diseases and putative treatments to better understand and alleviate a genetic disease or a condition, e.g., cancer.Type: GrantFiled: March 23, 2017Date of Patent: September 21, 2021Assignees: The Broad Institute, Inc., Massachusetts Institute of TechnologyInventors: Phillip A. Sharp, Feng Zhang, Randall Jeffrey Platt, Sidi Chen
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Patent number: 10946035Abstract: The invention relates in aspects to hybrid RNAs lacking a poly-A tail and nucleic acid vectors for expressing the RNA. The hybrid RNAs in some instances have a stabilizing triple helical structure. Related methods for expressing RNA in vivo and in vitro are also disclosed.Type: GrantFiled: July 31, 2017Date of Patent: March 16, 2021Assignee: Massachusetts Institute of TechnologyInventors: Jeremy E. Wilusz, Phillip A. Sharp
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Publication number: 20200270602Abstract: The present invention relates to a Drosophila in vitro system which was used to demonstrate that dsRNA is processed to RNA segments 21-23 nucleotides (nt) in length. Furthermore, when these 21-23 nt fragments are purified and added back to Drosophila extracts, they mediate RNA interference in the absence of long dsRNA, Thus, these 21-23 nt fragments are the sequence-specific mediators of RNA degradation. A molecular signal, which may be their specific length, must be present in these 21-23 nt fragments to recruit cellular factors involved in RNAi. This present invention encompasses these 21-23 nt fragments and their use for specifically inactivating gene function. The use of these fragments (or chemically synthesized oligonucleotides of the same or similar nature) enables the targeting of specific mRNAs for degradation in mammalian cells, where the use of long dsRNAs to elicit RNAi is usually not practical, presumably because of the deleterious effects of the interferon response.Type: ApplicationFiled: September 24, 2019Publication date: August 27, 2020Inventors: Thomas Tuschl, Phillip D. Zamore, Phillip A. Sharp, David P. Bartel
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Publication number: 20190390266Abstract: The present disclosure relates to a method of sequencing nascent RNA in a cell. In some embodiments, the nascent RNA is conjugated to DNA using copper-catalyzed azide-alkyne cycloaddition (CuAAC). Methods of the present disclosure can be used to generate genomic libraries of a cell and measure gene expression and enhancer and/or super-enhancer activity.Type: ApplicationFiled: March 29, 2019Publication date: December 26, 2019Applicant: Massachusetts Institute of TechnologyInventors: Phillip A. Sharp, Dig Mahat
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Patent number: 10472625Abstract: The present invention relates to a Drosophila in vitro system which was used to demonstrate that dsRNA is processed to RNA segments 21-23 nucleotides (nt) in length. Furthermore, when these 21-23 nt fragments are purified and added back to Drosophila extracts, they mediate RNA interference in the absence of long dsRNA. Thus, these 21-23 nt fragments are the sequence-specific mediators of RNA degradation. A molecular signal, which may be their specific length, must be present in these 21-23 nt fragments to recruit cellular factors involved in RNAi. This present invention encompasses these 21-23 nt fragments and their use for specifically inactivating gene function. The use of these fragments (or chemically synthesized oligonucleotides of the same or similar nature) enables the targeting of specific mRNAs for degradation in mammalian cells, where the use of long dsRNAs to elicit RNAi is usually not practical, presumably because of the deleterious effects of the interferon response.Type: GrantFiled: October 16, 2015Date of Patent: November 12, 2019Assignees: Max-Planck-Gesellschaft Zur Förderung Der Wissenschaften E.V., Massachusetts Institute of Technology, Whitehead Institute for Biomedical Research, University of MassachusettsInventors: Thomas Tuschl, Phillip D. Zamore, Phillip A. Sharp, David P. Bartel
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Publication number: 20180140625Abstract: The invention relates in aspects to hybrid RNAs lacking a poly-A tail and nucleic acid vectors for expressing the RNA. The hybrid RNAs in some instances have a stabilizing triple helical structure. Related methods for expressing RNA in vivo and in vitro are also disclosed.Type: ApplicationFiled: July 31, 2017Publication date: May 24, 2018Applicant: Massachusetts Institute of TechnologyInventors: Jeremy E. Wilusz, Phillip A. Sharp
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Publication number: 20180112255Abstract: The present invention relates to in vivo methods for modeling tumor formation and/or tumor evolution comprising the use of eukaryotic cells in which one or more genetic target locus has been altered by the CRISPR/Cas system, and which cells are transplanted in non-human eukaryote as a model system for tumor formation and tumor evolution. In particular in vivo genetic screening methods for identifying genes involved in tumorigenesis and metastasis are disclosed. The invention further relates to kits and components for practicing the methods, as well as materials obtainable by the methods, in particular tumor and metastasis samples and cells or cell lines derived therefrom. The invention also relates to diagnostic and therapeutic methods derived from the information obtained in the modeling methods.Type: ApplicationFiled: June 30, 2017Publication date: April 26, 2018Inventors: Sidi Chen, Randall Jeffrey Platt, Neville Espi Sanjana, Phillip A. Sharp, Feng Zhang
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Publication number: 20180010134Abstract: The invention involves inducing 3-50 or more mutations (e.g., any whole number between 3 and 50 of mutations, with it noted that in some embodiments there can be up to 16 different RNA(s), e.g., sgRNAs each having its own a promoter, in a vector, such as AAV, and that when each sgRNA does not have its own promoter, there can be twice to thrice that amount of different RNA(s), e.g., sgRNAs, e.g., 32 or even 48 different guides delivered by one vector) in transgenic Cas9 eukaryotes to model genetic disease, e.g. cancer. The invention comprehends testing putative treatments with such models, e.g., testing putative chemical compounds that may be pharmaceutically relevant for treatment or gene therapy that may be relevant for treatment, or combinations thereof. The invention allows for the study of genetic diseases and putative treatments to better understand and alleviate a genetic disease or a condition, e.g., cancer.Type: ApplicationFiled: March 23, 2017Publication date: January 11, 2018Inventors: PHILLIP A. SHARP, Feng Zhang, Randall Jeffrey Platt, Sidi Chen
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Patent number: 9717749Abstract: The invention relates in aspects to hybrid RNAs lacking a poly-A tail and nucleic acid vectors for expressing the RNA. The hybrid RNAs in some instances have a 3? terminal stabilizing triple helical structure. Related methods for expressing said RNAs in vivo and in vitro are also disclosed.Type: GrantFiled: October 16, 2013Date of Patent: August 1, 2017Assignee: Massachusetts Institute of TechnologyInventors: Jeremy E. Wilusz, Phillip A. Sharp
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Publication number: 20160251662Abstract: The invention provides methods for treating or decreasing the likelihood of developing a stress-granule related disorder and/or cancer by administering one or more poly-ADP-ribose polymerase (PARP) inhibitors, one or more PARP activators, one or more poly-ADP-ribose glycosylase (PARG) activators, and/or one or more poly-ADP-ribose glycohydrolase ARH3 activators. The invention also provides corresponding methods of decreasing stress granule formation and/or proliferation in a cell or a population of cells. The invention further provides methods of increasing the number of stress granules and proliferation in a cell or a population of cells by administering one or more PARP activators, one or more PARP inhibitors, one or more PARG inhibitors, and/or one or more ARH3 inhibitors.Type: ApplicationFiled: January 29, 2016Publication date: September 1, 2016Inventors: PAUL CHANG, SEJAL K. VYAS, ANTHONY LEUNG, PHILLIP A. SHARP
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Patent number: 9272022Abstract: The invention provides methods for treating or decreasing the likelihood of developing a stress-granule related disorder and/or cancer by administering one or more poly-ADP-ribose polymerase (PARP) inhibitors, one or more PARP activators, one or more poly-ADP-ribose glycosylase (PARG) activators, and/or one or more poly-ADP-ribose glycohydrolase ARH3 activators. The invention also provides corresponding methods of decreasing stress granule formation and/or proliferation in a cell or a population of cells. The invention further provides methods of increasing the number of stress granules and proliferation in a cell or a population of cells by administering one or more PARP activators, one or more PARP inhibitors, one or more PARG inhibitors, and/or one or more ARH3 inhibitors.Type: GrantFiled: March 30, 2012Date of Patent: March 1, 2016Assignee: Massachusetts Institute of TechnologyInventors: Paul Chang, Sejal K. Vyas, Anthony Leung, Phillip A. Sharp
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Publication number: 20160032288Abstract: The present invention relates to a Drosophila in vitro system which was used to demonstrate that dsRNA is processed to RNA segments 21-23 nucleotides (nt) in length. Furthermore, when these 21-23 nt fragments are purified and added back to Drosophila extracts, they mediate RNA interference in the absence of long dsRNA. Thus, these 21-23 nt fragments are the sequence-specific mediators of RNA degradation. A molecular signal, which may be their specific length, must be present in these 21-23 nt fragments to recruit cellular factors involved in RNAI. This present invention encompasses these 21-23 nt fragments and their use for specifically inactivating gene function. The use of these fragments (or chemically synthesized oligonucleotides of the same or similar nature) enables the targeting of specific mRNAs for degradation in mammalian cells, where the use of long dsRNAs to elicit RNAi is usually not practical, presumably because of the deleterious effects of the interferon response.Type: ApplicationFiled: October 16, 2015Publication date: February 4, 2016Inventors: Thomas Tuschl, Phillip D. Zamore, Phillip A. Sharp, David P. Bartel
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Patent number: 9193753Abstract: The present invention relates to a Drosophila in vitro system which was used to demonstrate that dsRNA is processed to RNA segments 21-23 nucleotides (nt) in length. Furthermore, when these 21-23 nt fragments are purified and added back to Drosophila extracts, they mediate RNA interference in the absence of long dsRNA. Thus, these 21-23 nt fragments are the sequence-specific mediators of RNA degradation. A molecular signal, which may be their specific length, must be present in these 21-23 nt fragments to recruit cellular factors involved in RNAi. This present invention encompasses these 21-23 nt fragments and their use for specifically inactivating gene function. The use of these fragments (or chemically synthesized oligonucleotides of the same or similar nature) enables the targeting of specific mRNAs for degradation in mammalian cells, where the use of long dsRNAs to elicit RNAi is usually not practical, presumably because of the deleterious effects of the interferon response.Type: GrantFiled: March 14, 2013Date of Patent: November 24, 2015Assignees: University of Massachusetts, Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Max-Planck-Gesellschaft Zur Förderung Der Wissenschaften E.V.Inventors: Thomas Tuschl, Phillip D. Zamore, Phillip A. Sharp, David P. Bartel
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Publication number: 20150315574Abstract: The invention relates in aspects to hybrid RNAs lacking a poly-A tail and nucleic acid vectors for expressing the RNA. The hybrid RNAs in some instances have a 3? terminal stabilizing triple helical structure. Related methods for expressing said RNAs in vivo and in vitro are also disclosed.Type: ApplicationFiled: October 16, 2013Publication date: November 5, 2015Applicant: Massachusetts Institute of TechnologyInventors: Jeremy E. Wilusz, Phillip A. Sharp
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Patent number: 9012621Abstract: The present invention relates to a Drosophila in vitro system which was used to demonstrate that dsRNA is processed to RNA segments 21-23 nucleotides (nt) in length. Furthermore, when these 21-23 nt fragments are purified and added back to Drosophila extracts, they mediate RNA interference in the absence of long dsRNA. Thus, these 21-23 nt fragments are the sequence-specific mediators of RNA degradation. A molecular signal, which may be their specific length, must be present in these 21-23 nt fragments to recruit cellular factors involved in RNAi. This present invention encompasses these 21-23 nt fragments and their use for specifically inactivating gene function. The use of these fragments (or chemically synthesized oligonucleotides of the same or similar nature) enables the targeting of specific mRNAs for degradation in mammalian cells, where the use of long dsRNAs to elicit RNAi is usually not practical, presumably because of the deleterious effects of the interferon response.Type: GrantFiled: January 18, 2011Date of Patent: April 21, 2015Assignees: Max-Planck-Gesellschaft zur Förderung der Wissenschaften E.V., Massachusetts Institute of Technology, Whitehead Institute for Biomedical Research, University of MassachusettsInventors: Thomas Tuschl, Phillip D. Zamore, Phillip A. Sharp, David P. Bartel