Patents by Inventor David B. Thompson
David B. Thompson 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: 11905623Abstract: Some aspects of the present disclosure provide methods for evolving recombinases to recognize target sequences that differ from the canonical recognition sequences. Some aspects of this disclosure provide evolved recombinases, e.g., recombinases that bind and recombine naturally-occurring target sequences, such as, e.g., target sequences within the human Rosa26 locus. Methods for using such recombinases for genetically engineering nucleic acid molecules in vitro and in vivo are also provided. Some aspects of this disclosure also provide libraries and screening methods for assessing the target site preferences of recombinases, as well as methods for selecting recombinases that bind and recombine a non-canonical target sequence with high specificity.Type: GrantFiled: August 10, 2021Date of Patent: February 20, 2024Assignee: President and Fellows of Harvard CollegeInventors: David R. Liu, David B. Thompson, Jeffrey L. Bessen
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Publication number: 20230056852Abstract: Some aspects of this disclosure provide compositions, methods, and kits for improving the specificity of RNA-programmable endonucleases, such as Cas9. Also provided are variants of Cas9, e.g., Cas9 dimers and fusion proteins, engineered to have improved specificity for cleaving nucleic acid targets. Also provided are compositions, methods, and kits for site-specific nucleic acid modification using Cas9 fusion proteins (e.g., nuclease-inactivated Cas9 fused to a nuclease catalytic domain or a recombinase catalytic domain). Such Cas9 variants are useful in clinical and research settings involving site-specific modification of DNA, for example, genomic modifications.Type: ApplicationFiled: September 30, 2022Publication date: February 23, 2023Applicant: President and Fellows of Harvard CollegeInventors: David R. Liu, John Paul Guilinger, David B. Thompson
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Publication number: 20220281941Abstract: Compositions and provided to induce cells of the inner ear to renter the cell cycle and to proliferate. In particular, hair cells are induced to proliferate by administration of a composition which activates the Myc and Notch. Supporting cells are induced to transdifferentiate to hair cells by inhibition of Myc and Notch activity or the activation of Atoh1. Methods of treatment include the intracellular delivery of these molecules to a specific therapeutic target.Type: ApplicationFiled: May 23, 2022Publication date: September 8, 2022Inventors: Zheng-Yi Chen, David R. Liu, Margie Li, David B. Thompson, John Zuris
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Publication number: 20220226503Abstract: Compositions are described for direct protein delivery into multiple cell types in the mammalian inner ear. The compositions are used to deliver protein(s) (such as gene editing factors) editing of genetic mutations associated with deafness or associated disorders thereof. The delivery of genome editing proteins for gene editing and correction of genetic mutations protect or restore hearing from genetic deafness. Methods of treatment include the intracellular delivery of these molecules to a specific therapeutic target.Type: ApplicationFiled: June 17, 2021Publication date: July 21, 2022Inventors: Zheng-Yi Chen, David R. Liu, Margie Li, David B. Thompson, John Zuris
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Patent number: 11370823Abstract: Compositions and provided to induce cells of the inner ear to renter the cell cycle and to proliferate. In particular, hair cells are induced to proliferate by administration of a composition which activates the Myc and Notch. Supporting cells are induced to transdifferentiate to hair cells by inhibition of Myc and Notch activity or the activation of Atoh1. Methods of treatment include the intracellular delivery of these molecules to a specific therapeutic target.Type: GrantFiled: October 29, 2015Date of Patent: June 28, 2022Assignees: Massachusetts Eye and Ear Infirmary, President and Fellows of Harvard CollegeInventors: Zheng-Yi Chen, David R. Liu, Margie Li, David B. Thompson, John Zuris
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Publication number: 20220073887Abstract: Some aspects of the present disclosure provide methods for evolving recombinases to recognize target sequences that differ from the canonical recognition sequences. Some aspects of this disclosure provide evolved recombinases, e.g., recombinases that bind and recombine naturally-occurring target sequences, such as, e.g., target sequences within the human Rosa26 locus. Methods for using such recombinases for genetically engineering nucleic acid molecules in vitro and in vivo are also provided. Some aspects of this disclosure also provide libraries and screening methods for assessing the target site preferences of recombinases, as well as methods for selecting recombinases that bind and recombine a non-canonical target sequence with high specificity.Type: ApplicationFiled: August 10, 2021Publication date: March 10, 2022Applicant: President and Fellows of Harvard CollegeInventors: David R. Liu, David B. Thompson, Jeffrey L. Bessen
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Publication number: 20210315994Abstract: Compositions, methods, strategies, kits, and systems for the delivery of negatively charged proteins, protein complexes, and fusion proteins, using cationic polymers or lipids are provided. Delivery of proteins into cells can be effected in vivo, ex vivo, or in vitro. Proteins that can be delivered using the compositions, methods, strategies, kits, and systems provided herein include, without limitation, enzymes, transcription factors, genome editing proteins, Cas9 proteins, TALEs, TALENs, nucleases, binding proteins (e.g., ligands, receptors, antibodies, antibody fragments; nucleic acid binding proteins, etc.), structural proteins, and therapeutic proteins (e.g., tumor suppressor proteins, therapeutic enzymes, growth factors, growth factor receptors, transcription factors, proteases, etc.), as well as variants and fusions of such proteins.Type: ApplicationFiled: December 22, 2020Publication date: October 14, 2021Applicant: President and Fellows of Harvard CollegeInventors: David R. Liu, David B. Thompson, John Anthony Zuris
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Patent number: 11104967Abstract: Some aspects of the present disclosure provide methods for evolving recombinases to recognize target sequences that differ from the canonical recognition sequences. Some aspects of this disclosure provide evolved recombinases, e.g., recombinases that bind and recombine naturally-occurring target sequences, such as, e.g., target sequences within the human Rosa26 locus. Methods for using such recombinases for genetically engineering nucleic acid molecules in vitro and in vivo are also provided. Some aspects of this disclosure also provide libraries and screening methods for assessing the target site preferences of recombinases, as well as methods for selecting recombinases that bind and recombine a non-canonical target sequence with high specificity.Type: GrantFiled: July 24, 2019Date of Patent: August 31, 2021Assignee: President and Fellows of Harvard CollegeInventors: David R. Liu, David B. Thompson, Jeffrey L. Bessen
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Patent number: 11071790Abstract: Compositions are described for direct protein delivery into multiple cell types in the mammalian inner ear. The compositions are used to deliver protein(s) (such as gene editing factors) editing of genetic mutations associated with deafness or associated disorders thereof. The delivery of genome editing proteins for gene editing and correction of genetic mutations protect or restore hearing from genetic deafness. Methods of treatment include the intracellular delivery of these molecules to a specific therapeutic target.Type: GrantFiled: October 29, 2015Date of Patent: July 27, 2021Assignees: Massachusetts Eye and Ear Infirmary, President and Fellows of Harvard CollegeInventors: Zheng-Yi Chen, David R. Liu, Margie Li, David B. Thompson, John Zuris
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Publication number: 20210214698Abstract: Some aspects of this disclosure provide compositions, methods, and kits for improving the specificity of RNA-programmable endonucleases, such as Cas9. Also provided are variants of Cas9, e.g., Cas9 dimers and fusion proteins, engineered to have improved specificity for cleaving nucleic acid targets. Also provided are compositions, methods, and kits for site-specific nucleic acid modification using Cas9 fusion proteins (e.g., nuclease-inactivated Cas9 fused to a nuclease catalytic domain or a recombinase catalytic domain). Such Cas9 variants are useful in clinical and research settings involving site-specific modification of DNA, for example, genomic modifications.Type: ApplicationFiled: November 24, 2020Publication date: July 15, 2021Applicant: President and Fellows of Harvard CollegeInventors: David R. Liu, John Paul Guilinger, David B. Thompson
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Patent number: 10912833Abstract: Compositions, methods, strategies, kits, and systems for the delivery of negatively charged proteins, protein complexes, and fusion proteins, using cationic polymers or lipids are provided. Delivery of proteins into cells can be effected in vivo, ex vivo, or in vitro. Proteins that can be delivered using the compositions, methods, strategies, kits, and systems provided herein include, without limitation, enzymes, transcription factors, genome editing proteins, Cas9 proteins, TALEs, TALENs, nucleases, binding proteins (e.g., ligands, receptors, antibodies, antibody fragments; nucleic acid binding proteins, etc.), structural proteins, and therapeutic proteins (e.g., tumor suppressor proteins, therapeutic enzymes, growth factors, growth factor receptors, transcription factors, proteases, etc.), as well as variants and fusions of such proteins.Type: GrantFiled: April 20, 2018Date of Patent: February 9, 2021Assignee: President and Fellows of Harvard CollegeInventors: David R. Liu, David B. Thompson, John Anthony Zuris
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Patent number: 10858639Abstract: Some aspects of this disclosure provide compositions, methods, and kits for improving the specificity of RNA-programmable endonucleases, such as Cas9. Also provided are variants of Cas9, e.g., Cas9 dimers and fusion proteins, engineered to have improved specificity for cleaving nucleic acid targets. Also provided are compositions, methods, and kits for site-specific nucleic acid modification using Cas9 fusion proteins (e.g., nuclease-inactivated Cas9 fused to a nuclease catalytic domain or a recombinase catalytic domain). Such Cas9 variants are useful in clinical and research settings involving site-specific modification of DNA, for example, genomic modifications.Type: GrantFiled: September 5, 2014Date of Patent: December 8, 2020Assignee: President and Fellows of Harvard CollegeInventors: David R. Liu, John Paul Guilinger, David B. Thompson
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Publication number: 20200323984Abstract: Compositions, methods, strategies, kits, and systems for the supercharged protein-mediated delivery of functional effector proteins into cells in vivo, ex vivo, or in vitro are provided. Compositions, methods, strategies, kits, and systems for delivery of functional effector proteins using cationic lipids and cationic polymers are also provided. Functional effector proteins include, without limitation, transcriptional modulators (e.g., repressors or activators), recombinases, nucleases (e.g., RNA-programmable nucleases, such as Cas9 proteins; TALE nuclease, and zinc finger nucleases), deaminases, and other gene modifying/editing enzymes. Functional effector proteins include TALE effector proteins, e.g., TALE transcriptional activators and repressors, as well as TALE nucleases.Type: ApplicationFiled: April 28, 2020Publication date: October 15, 2020Applicant: President and Fellows of Harvard CollegeInventors: Daivd R. Liu, John Anthony Zuris, David B. Thompson
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Patent number: 10682410Abstract: Compositions, methods, strategies, kits, and systems for the supercharged protein-mediated delivery of functional effector proteins into cells in vivo, ex vivo, or in vitro are provided. Compositions, methods, strategies, kits, and systems for delivery of functional effector proteins using cationic lipids and cationic polymers are also provided. Functional effector proteins include, without limitation, transcriptional modulators (e.g., repressors or activators), recombinases, nucleases (e.g., RNA-programmable nucleases, such as Cas9 proteins; TALE nuclease, and zinc finger nucleases), deaminases, and other gene modifying/editing enzymes. Functional effector proteins include TALE effector proteins, e.g., TALE transcriptional activators and repressors, as well as TALE nucleases.Type: GrantFiled: September 5, 2014Date of Patent: June 16, 2020Assignee: President and Fellows of Harvard CollegeInventors: David R. Liu, John Anthony Zuris, David B. Thompson
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Publication number: 20200071722Abstract: Some aspects of the present disclosure provide methods for evolving recombinases to recognize target sequences that differ from the canonical recognition sequences. Some aspects of this disclosure provide evolved recombinases, e.g., recombinases that bind and recombine naturally-occurring target sequences, such as, e.g., target sequences within the human Rosa26 locus. Methods for using such recombinases for genetically engineering nucleic acid molecules in vitro and in vivo are also provided. Some aspects of this disclosure also provide libraries and screening methods for assessing the target site preferences of recombinases, as well as methods for selecting recombinases that bind and recombine a non-canonical target sequence with high specificity.Type: ApplicationFiled: July 24, 2019Publication date: March 5, 2020Applicant: President and Fellows of Harvard CollegeInventors: David R. Liu, David B. Thompson, Jeffrey L. Bessen
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Patent number: 10392674Abstract: Some aspects of the present disclosure provide methods for evolving recombinases to recognize target sequences that differ from the canonical recognition sequences. Some aspects of this disclosure provide evolved recombinases, e.g., recombinases that bind and recombine naturally-occurring target sequences, such as, e.g., target sequences within the human Rosa26 locus. Methods for using such recombinases for genetically engineering nucleic acid molecules in vitro and in vivo are also provided. Some aspects of this disclosure also provide libraries and screening methods for assessing the target site preferences of recombinases, as well as methods for selecting recombinases that bind and recombine a non-canonical target sequence with high specificity.Type: GrantFiled: July 22, 2016Date of Patent: August 27, 2019Assignee: President and Fellows of Harvard CollegeInventors: David R. Liu, David B. Thompson, Jeffrey L. Bessen
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Patent number: 10258697Abstract: Compositions are described for direct protein delivery into multiple cell types in the mammalian inner ear. The compositions are used to deliver protein(s) (such as gene editing factors) editing of genetic mutations associated with deafness or associated disorders thereof. The delivery of genome editing proteins for gene editing and correction of genetic mutations protect or restore hearing from genetic deafness. Methods of treatment include the intracellular delivery of these molecules to a specific therapeutic target.Type: GrantFiled: October 29, 2015Date of Patent: April 16, 2019Assignee: Massachusetts Eye and Ear InfirmaryInventors: Zheng-Yi Chen, David Liu, John Anthony Zuris, David B. Thompson
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Publication number: 20180312542Abstract: The inefficient delivery of proteins into mammalian cells remains a major barrier to realizing the therapeutic potential of many proteins. Previously, it has been demonstrated that superpositively charged proteins are efficiently endocytosed and can bring associated proteins and nucleic acids into cells. The vast majority of cargo delivered in this manner, however, remains in endosomes and does not reach the cytosol. The present invention provides endosomal escape peptides that enhance endosomal escape and cytosolic delivery of proteins and other agents of interest. In one aspect, described herein are novel fusion proteins comprising endosomal escape peptides fused to proteins and other agents of interest for delivery to a cell. Also provided herein are methods and compounds useful in preparing the fusion proteins, as well as pharmaceutical compositions and uses of the fusion proteins.Type: ApplicationFiled: October 19, 2016Publication date: November 1, 2018Applicant: President and Fellows of Harvard CollegeInventors: David R. Liu, Margie Li, David B. Thompson
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Publication number: 20180236081Abstract: Compositions, methods, strategies, kits, and systems for the delivery of negatively charged proteins, protein complexes, and fusion proteins, using cationic polymers or lipids are provided. Delivery of proteins into cells can be effected in vivo, ex vivo, or in vitro. Proteins that can be delivered using the compositions, methods, strategies, kits, and systems provided herein include, without limitation, enzymes, transcription factors, genome editing proteins, Cas9 proteins, TALEs, TALENs, nucleases, binding proteins (e.g., ligands, receptors, antibodies, antibody fragments; nucleic acid binding proteins, etc.), structural proteins, and therapeutic proteins (e.g., tumor suppressor proteins, therapeutic enzymes, growth factors, growth factor receptors, transcription factors, proteases, etc.), as well as variants and fusions of such proteins.Type: ApplicationFiled: April 20, 2018Publication date: August 23, 2018Applicant: President and Fellows of Harvard CollegeInventors: David R. Liu, David B. Thompson, John Anthony Zuris
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Patent number: 9999671Abstract: Compositions, methods, strategies, kits, and systems for the delivery of negatively charged proteins, protein complexes, and fusion proteins, using cationic polymers or lipids are provided. Delivery of proteins into cells can be effected in vivo, ex vivo, or in vitro. Proteins that can be delivered using the compositions, methods, strategies, kits, and systems provided herein include, without limitation, enzymes, transcription factors, genome editing proteins, Cas9 proteins, TALEs, TALENs, nucleases, binding proteins (e.g., ligands, receptors, antibodies, antibody fragments; nucleic acid binding proteins, etc.), structural proteins, and therapeutic proteins (e.g., tumor suppressor proteins, therapeutic enzymes, growth factors, growth factor receptors, transcription factors, proteases, etc.), as well as variants and fusions of such proteins.Type: GrantFiled: October 30, 2014Date of Patent: June 19, 2018Assignee: President and Fellows of Harvard CollegeInventors: David R. Liu, David B. Thompson, John Anthony Zuris