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).

  • Patent number: 10258697
    Abstract: 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: Grant
    Filed: October 29, 2015
    Date of Patent: April 16, 2019
    Assignee: Massachusetts Eye and Ear Infirmary
    Inventors: Zheng-Yi Chen, David Liu, John Anthony Zuris, David B. Thompson
  • Publication number: 20180312542
    Abstract: 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: Application
    Filed: October 19, 2016
    Publication date: November 1, 2018
    Applicant: President and Fellows of Harvard College
    Inventors: David R. Liu, Margie Li, David B. Thompson
  • Publication number: 20180236081
    Abstract: 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: Application
    Filed: April 20, 2018
    Publication date: August 23, 2018
    Applicant: President and Fellows of Harvard College
    Inventors: David R. Liu, David B. Thompson, John Anthony Zuris
  • Patent number: 9999671
    Abstract: 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: Grant
    Filed: October 30, 2014
    Date of Patent: June 19, 2018
    Assignee: President and Fellows of Harvard College
    Inventors: David R. Liu, David B. Thompson, John Anthony Zuris
  • Patent number: 9737604
    Abstract: 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: Grant
    Filed: August 18, 2014
    Date of Patent: August 22, 2017
    Assignee: President and Fellows of Harvard College
    Inventors: David R. Liu, John Anthony Zuris, David B. Thompson
  • Publication number: 20170044520
    Abstract: 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: Application
    Filed: July 22, 2016
    Publication date: February 16, 2017
    Inventors: David R. Liu, David B. Thompson, Jeffrey L. Bessen
  • Patent number: 9526784
    Abstract: 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 funcational 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: Grant
    Filed: August 18, 2014
    Date of Patent: December 27, 2016
    Assignee: President and Fellows of Harvard College
    Inventors: David R. Liu, John Anthony Zuris, David B. Thompson
  • Publication number: 20160280748
    Abstract: Compositions, preparations, systems, and related methods for delivering a supercharged protein, or a complex of a supercharged protein and an agent (e.g., nucleic acids, peptides, proteins, small molecules) to cells are provided. Such systems and methods include the use of supercharged proteins. For example, superpositively charged proteins may be associated with nucleic acids (which typically have a net negative charge) via electrostatic interactions. In some embodiments, such systems and methods involve altering the primary sequence of a protein in order to “supercharge” the protein (e.g., to generate a superpositively-charged protein). In some embodiments, complexes comprising supercharged proteins and one or more agents to be delivered are useful as therapeutic agents. In some embodiments, complexes and/or pharmaceutical compositions thereof are administered to a subject in need thereof.
    Type: Application
    Filed: December 29, 2015
    Publication date: September 29, 2016
    Applicant: President and Fellows of Harvard College
    Inventors: David R. Liu, Brian R. McNaughton, James Joseph Cronican, David B. Thompson
  • Publication number: 20160215276
    Abstract: 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: Application
    Filed: September 5, 2014
    Publication date: July 28, 2016
    Applicant: President and Fellows of Harvard College
    Inventors: David R. Liu, John Paul Guilinger, David B. Thompson
  • Publication number: 20160200779
    Abstract: 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: Application
    Filed: September 5, 2014
    Publication date: July 14, 2016
    Applicant: President and Fellows of Harvard College
    Inventors: David R. LIU, John Anthony ZURIS, David B. THOMPSON
  • Patent number: 9388430
    Abstract: 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 recombination, using Cas9 fusion proteins (e.g., nuclease-inactivated Cas9 fused to 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: Grant
    Filed: June 30, 2014
    Date of Patent: July 12, 2016
    Assignee: President and Fellows of Harvard College
    Inventors: David R. Liu, John Paul Guilinger, David B. Thompson
  • Patent number: 9322037
    Abstract: 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). Such Cas9 variants are useful in clinical and research settings involving site-specific modification of DNA, for example, genomic modifications.
    Type: Grant
    Filed: June 30, 2014
    Date of Patent: April 26, 2016
    Assignee: President and Fellows of Harvard College
    Inventors: David R. Liu, John Paul Guilinger, David B. Thompson
  • Patent number: 9221886
    Abstract: Compositions, preparations, systems, and related methods for delivering a supercharged protein, or a complex of a supercharged protein and an agent (e.g., nucleic acids, peptides, proteins, small molecules) to cells are provided. Such systems and methods include the use of supercharged proteins. For example, superpositively charged proteins may be associated with nucleic acids (which typically have a net negative charge) via electrostatic interactions. In some embodiments, such systems and methods involve altering the primary sequence of a protein in order to “supercharge” the protein (e.g., to generate a superpositively-charged protein). In some embodiments, complexes comprising supercharged proteins and one or more agents to be delivered are useful as therapeutic agents. In some embodiments, complexes and/or pharmaceutical compositions thereof are administered to a subject in need thereof.
    Type: Grant
    Filed: April 28, 2010
    Date of Patent: December 29, 2015
    Assignee: President and Fellows of Harvard College
    Inventors: David R. Liu, Brian R. McNaughton, James Joseph Cronican, David B. Thompson
  • Publication number: 20150118216
    Abstract: 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: Application
    Filed: October 30, 2014
    Publication date: April 30, 2015
    Applicant: President and Fellows of Harvard College
    Inventors: David R. Liu, David B. Thompson, John Anthony Zuris
  • Publication number: 20150071898
    Abstract: 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 recombination, using Cas9 fusion proteins (e.g., nuclease-inactivated Cas9 fused to 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: Application
    Filed: June 30, 2014
    Publication date: March 12, 2015
    Applicant: President and Fellows of Harvard College
    Inventors: David R. Liu, John Paul Guilinger, David B. Thompson
  • Publication number: 20150071906
    Abstract: 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 funcational 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: Application
    Filed: August 18, 2014
    Publication date: March 12, 2015
    Applicant: President and Fellows of Harvard College
    Inventors: David R. Liu, John Anthony Zuris, David B. Thompson
  • Publication number: 20150071903
    Abstract: 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: Application
    Filed: August 18, 2014
    Publication date: March 12, 2015
    Applicant: President and Fellows of Harvard College
    Inventors: David R. Liu, John Anthony Zuris, David B. Thompson
  • Publication number: 20150071899
    Abstract: 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). Such Cas9 variants are useful in clinical and research settings involving site-specific modification of DNA, for example, genomic modifications.
    Type: Application
    Filed: June 30, 2014
    Publication date: March 12, 2015
    Applicant: President and Fellows of Harvard College
    Inventors: David R. Liu, John Paul Guilinger, David B. Thompson
  • Publication number: 20120100569
    Abstract: Compositions, preparations, systems, and related methods for delivering a supercharged protein, or a complex of a supercharged protein and an agent (e.g., nucleic acids, peptides, proteins, small molecules) to cells are provided. Such systems and methods include the use of supercharged proteins. For example, superpositively charged proteins may be associated with nucleic acids (which typically have a net negative charge) via electrostatic interactions. In some embodiments, such systems and methods involve altering the primary sequence of a protein in order to “supercharge” the protein (e.g., to generate a superpositively-charged protein). In some embodiments, complexes comprising supercharged proteins and one or more agents to be delivered are useful as therapeutic agents. In some embodiments, complexes and/or pharmaceutical compositions thereof are administered to a subject in need thereof.
    Type: Application
    Filed: April 28, 2010
    Publication date: April 26, 2012
    Inventors: David R. Liu, Brian R. McNaughton, James Joseph Cronican, David B. Thompson
  • Publication number: 20110112040
    Abstract: Compositions, systems and related methods for delivering a supercharged protein or a complex of a supercharged protein and therapeutic agent (e g, nucleic acid, peptide, small molecule) to cells are disclosed. Superpositively charged proteins may be associated with nucleic acids (which typically have a net negative charge) via electrostatic interactions. The systems and methods may involve altering the primary sequence of a protein in order to “supercharge” the protein (e g, to generate a superpositively-charged protein). The compositions may be used to treat proliferative diseases, infectious diseases, cardiovascular diseases, inborn errors in metabolism, genetic diseases, etc.
    Type: Application
    Filed: April 28, 2009
    Publication date: May 12, 2011
    Applicant: President and Fellows of Harvard College
    Inventors: David R. Liu, Brian R. Mcnaughton, James Joseph Cronican, David B. Thompson