Patents by Inventor Erik J. Sontheimer
Erik J. Sontheimer 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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Publication number: 20240067982Abstract: Disclosed are components and methods for RNA-directed DNA cleavage and gene editing. The components include and the methods utilize a Cas9 protein from Neisseria and one or more RNA molecules in order to direct the Cas9 protein to bind to and optionally cleave or nick a target sequence.Type: ApplicationFiled: November 23, 2022Publication date: February 29, 2024Inventors: Erik J. Sontheimer, Yan Zhang, Alfonzo Mondragon, Rakhi Rajan, James Thomson, Zhonggang Hou
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Publication number: 20230132569Abstract: Many strains of the human pathogen Neisseria meningitidis carry a compact Cas9 (NmeCas9) that can serve to limit genetic exchange via natural transformation. Cas9 orthologues (including NmeCas9) have recently been adopted for RNA-guided genome engineering and DNA binding, adding to the need to define better their activities and properties. The present invention examines DNA cleavage activities and substrate requirements of NmeCas9, including a set of unusually complex PAM recognition patterns. Unexpectedly, NmeCas9 is found able to cleave single-stranded DNA (ssDNA) targets in a manner that is RNA-guided but both PAM- and tracrRNA-independent. Beyond the requirement for guide-target pairing, this activity has no apparent sequence requirements, and the cleavage sites are measured from the 5? end of the DNA substrate's RNA-paired region.Type: ApplicationFiled: July 21, 2022Publication date: May 4, 2023Inventors: Erik J. Sontheimer, Yan Zhang
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Patent number: 11530394Abstract: The present invention is related to the field of CRISPR-Cas9 gene editing platforms. In particular, the present invention has identified Type II-C Cas9 anti-CRISPR (Acr) inhibitors that control Cas9 gene editing activity. Co-administration of such Acr inhibitors may provide an advantageous adjunct in permitting safe and practical biological therapeutics through spatial or temporal control of Cas9 activity; controlling Cas9-based gene drives in wild populations to reduce the ecological consequences of such forced inheritance schemes; and contributing to general research into various biotechnological, agricultural, and medical applications of gene editing technologies.Type: GrantFiled: March 13, 2017Date of Patent: December 20, 2022Assignees: UNIVERSITY OF MASSACHUSETTS, THE GOVERNING COUNCIL OF THE UNIVERSITY OF TORONTOInventors: Erik J. Sontheimer, Alan Davidson, Karen Maxwell, April Pawluk, Yan Zhang, Jooyoung Lee, Nadia Amrani
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Publication number: 20220389447Abstract: The present invention is related to compositions and methods for gene therapy. Several approaches described herein utilize the Neisseria meningitidis Cas9 system that provides a hyperaccurate CRISPR gene editing platform. Furthermore, the invention incorporates full length and truncated single guide RNA sequences that permit a complete sgRNA-Nme1Cas9 vector to be inserted into an adeno-associated viral plasmid that is compatible for in vivo administration. Furthermore, Type II-C Cas9 orthologs have been identified that target protospacer adjacent motif sequences limited to between one-four required nucleotides.Type: ApplicationFiled: November 9, 2018Publication date: December 8, 2022Inventors: Erik J. Sontheimer, Raed Ibraheim, Wen Xue, Aamir Mir, Alireza Edraki, Ildar Gainetdinov
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Patent number: 11453864Abstract: Many strains of the human pathogen Neisseria meningitidis carry a compact Cas9 (NmeCas9) that can serve to limit genetic exchange via natural transformation. Cas9 orthologues (including NmeCas9) have recently been adopted for RNA-guided genome engineering and DNA binding, adding to the need to define better their activities and properties. The present invention examines DNA cleavage activities and substrate requirements of NmeCas9, including a set of unusually complex PAM recognition patterns. Unexpectedly, NmeCas9 is found able to cleave single-stranded DNA (ssDNA) targets in a manner that is RNA-guided but both PAM- and tracrRNA-independent. Beyond the requirement for guide-target pairing, this activity has no apparent sequence requirements, and the cleavage sites are measured from the 5? end of the DNA substrate's RNA-paired region.Type: GrantFiled: September 6, 2016Date of Patent: September 27, 2022Assignee: UNIVERSITY OF MASSACHUSETTSInventors: Erik J. Sontheimer, Yan Zhang
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Publication number: 20220290113Abstract: The present invention is related to the field of gene editing. In particular, the gene editing is directed toward single nucleotide base editing. For example, such single nucleotide base editing results in a conversion of a OG base pair to a T*A base pair. The high accuracy and precision of the presently disclosed single nucleotide base gene editor is accomplished by an NmeCas9 nuclease that is fused to a nucleotide deaminase protein. The compact nature of the NmeCas9 coupled with a larger number of compatible protospacer adjacent motifs provide the Cas9 fusion constructs contemplated herein to have a gene editing window that can edit sites that are not targetable by other conventional SpyCas9 base editor platforms.Type: ApplicationFiled: October 15, 2019Publication date: September 15, 2022Inventors: Erik J. Sontheimer, Xin Gao, Aamir Mir, Alireza Edraki, Scot A. Wolfe, Pengpeng Liu
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Publication number: 20210395710Abstract: The present invention provides a Cas9 platform to facilitate single-site nuclease gene editing precision within a human genome. For example, a Cas9 nuclease/DNA-targeting unit (Cas9-DTU) fusion protein precisely delivers a Cas9/sgRNA complex to a specific target site within the genome for subsequent sgRNA-dependent cleavage of an adjacent target sequence. Alternatively, attenuating Cas9 binding using mutations to the a protospacer adjacent motif (PAM) recognition domain makes Cas9 target site recognition dependent on the associated DTU, all while retaining Cas9's sgRNA-mediated DNA cleavage fidelity. Cas9-DTU fusion proteins have improved target site binding precision, greater nuclease activity, and a broader sequence targeting range than standard Cas9 systems. Existing Cas9 or sgRNA variants (e.g., truncated sgRNAs (tru-gRNAs), nickases and FokI fusions) are compatible with these improvements to further reduce off-target cleavage.Type: ApplicationFiled: May 6, 2021Publication date: December 23, 2021Inventors: Scot A Wolfe, Mehmet Fatih Bolukbasi, Ankit Gupta, Erik J. Sontheimer, Nadia Amrani
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Patent number: 11028380Abstract: The present invention provides a Cas9 platform to facilitate single-site nuclease gene editing precision within a human genome. For example, a Cas9 nuclease/DNA-targeting unit (Cas9-DTU) fusion protein precisely delivers a Cas9/sgRNA complex to a specific target site within the genome for subsequent sgRNA-dependent cleavage of an adjacent target sequence. Alternatively, attenuating Cas9 binding using mutations to the a protospacer adjacent motif (PAM) recognition domain makes Cas9 target site recognition dependent on the associated DTU, all while retaining Cas9's sgRNA-mediated DNA cleavage fidelity. Cas9-DTU fusion proteins have improved target site binding precision, greater nuclease activity, and a broader sequence targeting range than standard Cas9 systems. Existing Cas9 or sgRNA variants (e.g., truncated sgRNAs (tru-gRNAs), nickases and FokI fusions) are compatible with these improvements to further reduce off-target cleavage.Type: GrantFiled: December 19, 2018Date of Patent: June 8, 2021Assignee: University of MassachusettsInventors: Scot Andrew Wolfe, Mehmet Fatih Bolukbasi, Ankit Gupta, Erik J Sontheimer, Nadia Amrani
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Publication number: 20190382741Abstract: The present invention is related to the field of CRISPR-Cas9 gene editing platforms. In particular, the present invention has identified Type II-C Cas9 anti-CRISPR (Acr) inhibitors that control Cas9 gene editing activity. Co-administration of such Acr inhibitors may provide an advantageous adjunct in permitting safe and practical biological therapeutics through spatial or temporal control of Cas9 activity; controlling Cas9-based gene drives in wild populations to reduce the ecological consequences of such forced inheritance schemes; and contributing to general research into various biotechnological, agricultural, and medical applications of gene editing technologies.Type: ApplicationFiled: March 13, 2017Publication date: December 19, 2019Inventors: Erik J. Sontheimer, Alan Davidson, Karen Maxwell
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Publication number: 20190338308Abstract: The present invention is related to compositions and methods for gene therapy. Several approaches described herein utilize the Neisseria meningitidis Cas9 system that provides a hyperaccurate CRISPR gene editing platform. Furthermore, the invention incorporates full length and truncated single guide RNA sequences that permit a complete sgRNA-Nme1Cas9 vector to be inserted into an adeno-associated viral plasmid that is compatible for in vivo administration. Furthermore, Type II-C Cas9 orthologs have been identified that target protospacer adjacent motif sequences limited to between one-four required nucleotides.Type: ApplicationFiled: November 9, 2018Publication date: November 7, 2019Inventors: Erik J. Sontheimer, Raed Ibraheim, Wen Xue, Aamir Mir, Alireza Edraki, Ildar Gainetdinov
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Publication number: 20190276810Abstract: The present invention provides a Cas9 platform to facilitate single-site nuclease gene editing precision within a human genome. For example, a Cas9 nuclease/DNA-targeting unit (Cas9-DTU) fusion protein precisely delivers a Cas9/sgRNA complex to a specific target site within the genome for subsequent sgRNA-dependent cleavage of an adjacent target sequence. Alternatively, attenuating Cas9 binding using mutations to the a protospacer adjacent motif (PAM) recognition domain makes Cas9 target site recognition dependent on the associated DTU, all while retaining Cas9's sgRNA-mediated DNA cleavage fidelity. Cas9-DTU fusion proteins have improved target site binding precision, greater nuclease activity, and a broader sequence targeting range than standard Cas9 systems. Existing Cas9 or sgRNA variants (e.g., truncated sgRNAs (tru-gRNAs), nickases and FokI fusions) are compatible with these improvements to further reduce off-target cleavage.Type: ApplicationFiled: December 19, 2018Publication date: September 12, 2019Inventors: Scot A. Wolfe, Mehmet Fatih Bolukbasi, Ankit Gupta, Erik J. Sontheimer, Nadia Amrani
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Patent number: 10190106Abstract: The present invention provides a Cas9 platform to facilitate single-site nuclease gene editing precision within a human genome. For example, a Cas9 nuclease/DNA-targeting unit (Cas9-DTU) fusion protein precisely delivers a Cas9/sgRNA complex to a specific target site within the genome for subsequent sgRNA-dependent cleavage of an adjacent target sequence. Alternatively, attenuating Cas9 binding using mutations to the a protospacer adjacent motif (PAM) recognition domain makes Cas9 target site recognition dependent on the associated DTU, all while retaining Cas9's sgRNA-mediated DNA cleavage fidelity. Cas9-DTU fusion proteins have improved target site binding precision, greater nuclease activity, and a broader sequence targeting range than standard Cas9 systems. Existing Cas9 or sgRNA variants (e.g., truncated sgRNAs (tru-gRNAs), nickases and FokI fusions) are compatible with these improvements to further reduce off-target cleavage.Type: GrantFiled: December 21, 2015Date of Patent: January 29, 2019Assignee: Univesity of MassachusettsInventors: Scot Andrew Wolfe, Mehmet Fatih Bolukbasi, Ankit Gupta, Erik J Sontheimer, Nadia Amrani
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Publication number: 20180355331Abstract: Many strains of the human pathogen Neisseria meningitidis carry a compact Cas9 (NmeCas9) that can serve to limit genetic exchange via natural transformation. Cas9 orthologues (including NmeCas9) have recently been adopted for RNA-guided genome engineering and DNA binding, adding to the need to define better their activities and properties. The present invention examines DNA cleavage activities and substrate requirements of NmeCas9, including a set of unusually complex PAM recognition patterns. Unexpectedly, NmeCas9 is found able to cleave single-stranded DNA (ssDNA) targets in a manner that is RNA-guided but both PAM- and tracrRNA-independent. Beyond the requirement for guide-target pairing, this activity has no apparent sequence requirements, and the cleavage sites are measured from the 5? end of the DNA substrate's RNA-paired region.Type: ApplicationFiled: September 6, 2016Publication date: December 13, 2018Inventors: Erik J. SONTHEIMER, Yan ZHANG
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Publication number: 20160177278Abstract: The present invention provides a Cas9 platform to facilitate single-site nuclease gene editing precision within a human genome. For example, a Cas9 nuclease/DNA-targeting unit (Cas9-DTU) fusion protein precisely delivers a Cas9/sgRNA complex to a specific target site within the genome for subsequent sgRNA-dependent cleavage of an adjacent target sequence. Alternatively, attenuating Cas9 binding using mutations to the a protospacer adjacent motif (PAM) recognition domain makes Cas9 target site recognition dependent on the associated DTU, all while retaining Cas9's sgRNA-mediated DNA cleavage fidelity. Cas9-DTU fusion proteins have improved target site binding precision, greater nuclease activity, and a broader sequence targeting range than standard Cas9 systems. Existing Cas9 or sgRNA variants (e.g., truncated sgRNAs (tru-gRNAs), nickases and FokI fusions) are compatible with these improvements to further reduce off-target cleavage.Type: ApplicationFiled: December 21, 2015Publication date: June 23, 2016Inventors: Scot Andrew Wolfe, Mehmet Fatih Bolukbasi, Ankit Gupta, Erik J. Sontheimer, Nadia Amrani
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Publication number: 20140349405Abstract: Disclosed are components and methods for RNA-directed DNA cleavage and gene editing. The components include and the methods utilize a Cas9 protein from Neisseria and one or more RNA molecules in order to direct the Cas9 protein to bind to and optionally cleave or nick a target sequence.Type: ApplicationFiled: May 22, 2014Publication date: November 27, 2014Applicants: WISCONSIN ALUMNI RESEARCH FOUNDATION, NORTHWESTERN UNIVERSITYInventors: Erik J. Sontheimer, Yan Zhang, Alfonso Mondragon, Rakhi Rajan, James Thomson, Zhonggang Hou
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Publication number: 20100076057Abstract: The present invention provides methods, systems, and compositions for interfering with the function and/or presence of a target DNA sequence in a eukaryotic cell (e.g., located in vitro or in a subject) using crRNA and CRISPR-associated (cas) proteins or cas encoding nucleic acids. The present invention also relates to a method for interfering with horizontal gene transfer based on the use of clustered, regularly interspaced short palindromic repeat (CRISPR) sequences.Type: ApplicationFiled: September 23, 2009Publication date: March 25, 2010Applicant: Northwestern UniversityInventors: Erik J. Sontheimer, Luciano A. Marraffini