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Patents

Mario R. Capecchi Ph.D.

The Nobel Prize in Physiology or Medicine 2007
Nobel prize also awarded to Sir Martin J. Evans and Oliver Smithies
National Medal of Science - Biological Sciences 2001

Molecular Geneticist. Introduced specific gene modifications in mice by using embryonic stem cells. Gene Targeting, Homeobox Genes, Development, Behavior.

Mother incarcerated as political prisoner, Germany. "At age 4½, I set off on my own, living in streets, orphanages; joining gangs of homeless children; generally hungry. Vivid recollections, brutal beyond description."

Patents

Publication:1/16
Publication No:US 4,687,737 A
Title:Mammalian suppressor genes
Publication Type:United States Utility Patent
Publication Date:Aug. 18, 1987
Filing Date:July 02, 1985
Inventors:Phillip A. Sharp, Newton, Massachusetts (US); Mario R. Capecchi, Salt Lake City, Utah (US); Uttam L. Raj Bhandary, Lexington, Massachusetts (US); and Frank A. Laski, Southfield, Michigan (US)
Assignee:Massachusetts Institute of Technology, Cambridge, Massachusetts
Abstract:A method of suppressing a nonsense codon in a gene in a mammalian cell by preparing an oligonucleotide primer having a mismatched anticodon region corresponding to the nonsense codon; preparing a DNA template for production of a tRNA molecule enabling the insertion of an amino acid when the nonsense codon is translated; forming a suppressor gene from said template and primer by site specific mutagenesis; and transforming the suppressor gene into the cell.
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Publication:2/16
Publication No:US 5,464,764 A
Title:Positive-negative selection methods and vectors
Publication Type:United States Utility Patent
Publication Date:Nov 07, 1995
Filing Date:Feb. 04, 1993
Inventors:Mario R. Capecchi, Salt Lake City, Utah (US); and Kirk R. Thomas, Salt Lake City, Utah (US)
Assignee:University of Utah Research Foundation, Salt Lake City, Utah
Abstract:Positive-negative selector (PNS) vectors are provided for modifying a target DNA sequence contained in the genome of a target cell capable of homologous recombination. The vector comprises a first DNA sequence which contains at least one sequence portion which is substantially homologous to a portion of a first region of a target DNA sequence. The vector also includes a second DNA sequence containing at least one sequence portion which is substantially homologous to another portion of a second region of a target DNA sequence. A third DNA sequence is positioned between the first and second DNA sequences and encodes a positive selection marker which when expressed is functional in the target cell in which the vector is used. A fourth DNA sequence encoding a negative selection marker, also functional in the target cell, is positioned 5' to the first or 3' to the second DNA sequence and is substantially incapable of homologous recombination with the target DNA sequence. The invention also includes transformed cells containing at least one predetermined modification of a target DNA sequence contained in the genome of the cell. In addition, the invention includes organisms such as non-human transgenic animals and plants which contain cells having predetermined modifications of a target DNA sequence in the genome of the organism.
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Publication:3/16
Publication No:US 2004/0197317 A1
Title:Persistent expression of candidate molecule in proliferating stem and progenitor cells for delivery of therapeutic products
Publication Type:Patent Application Publication
Publication Date:Oct. 07, 2004
Filing Date:Feb. 27, 2004
Inventors:Mahendra S. Rao, Timonium MD (US); Mario R. Capecchi
Assignee:
Abstract:A method of obtaining and the resulting isolated progenitor or stem cell population of proliferating cells persistently expressing a candidate molecule. Further, novel methods of ex vivo gene product (e.g., protein) production and treating symptoms of neurological or neurodegenerative disorders are also provided.
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Publication:4/16
Publication No:US2004/0197353 A1
Title:Population of hoxb8 mutants and uses in identifying agents for treating repetitive behaviors
Publication Type:Patent Application Publication
Publication Date:Oct. 07, 2004
Filing Date:May 21, 2004
Inventors:Joy M. Greer, Salt Lake City UT (US); Mario R. Capecchi
Assignee:
Abstract:This invention provides in vivo and in vitro methods of screening for an agent or a combination of agents that reduces one or more repetitive behaviors, comprising contacting neuronal cells of an animal with a HOXB8 gene mutation with the agent combination of agents to be screened, and determining whether one or more repetitive behaviors of the animal is reduced or whether one or more biochemical correlates of repetitive behaviors is reduced, the reduction in one or more repetitive behaviors or biochemical correlates indicating an agent or combination of agents that reduces repetitive behaviors. The invention also provides method of treating a subject with repetitive behaviors, comprising administering a therapeutically effective dose of the agent or combination of agents identified by the screening method. Further provided is a population of animals with a HOXB8 gene mutation, wherein more than 30% of the animals have excessive grooming behaviors and wherein less than 10% of the animals show skeletal defects.
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Publication:5/16
Publication No:US 2005/0048041 A1
Title:Persistent expression of candidate molecule in proliferating stem and progenitor cells for delivery of therapeutic products
Publication Type:Patent Application Publication
Publication Date:Mar. 3, 2005
Filing Date:Jun. 15, 2004
Inventors:Mahendra S. Rao, Timonium MD (US); Mario R. Capecchi
Assignee:
Abstract:A method of obtaining and the resulting isolated progenitor or stem cell population of proliferating cells persistently expressing a candidate molecule. Further, novel methods of ex vivo gene product (e.g., protein) production and treating symptoms of neurological or neurodegenerative disorders are also provided.
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Publication:6/16
Publication No:US 2005/0149998 A1
Title:Cells and non-human organisms containing predetermined genomic modifications and positive-negative selection methods and vectors for making same
Publication Type:Patent Application Publication
Publication Date:July 7, 2005
Filing Date:Dec. 23, 2003
Inventors:Mario R. Capecchi, Salt Lake City, UT (US); Kirk R. Thomas, Salt Lake City, UT (US)
Assignee:
Abstract:Positive-negative selector (PNS) vectors are provided for modifying a target DNA sequence contained in the genome of a target cell capable of homologous recombination. The vector comprises a first DNA sequence which contains at least one sequence portion which is substantially homologous to a portion of a first region of a target DNA sequence. The vector also includes a second DNA sequence containing at least one sequence portion which is substantially homologous to another portion of a second region of a target DNA sequence. A third DNA sequence is positioned between the first and second DNA sequences and encodes a positive selection marker which when expressed is functional in the target cell in which the vector is used. A fourth DNA sequence encoding a negative selection marker, also functional in the target cell, is positioned 5' to the first or 3' to the second DNA sequence and is substantially incapable of homologous recombination with the target DNA sequence. The invention also includes transformed cells containing at least one predetermined modification of a target DNA sequence contained in the genome of the cell. In addition, the invention includes organisms such as non-human transgenic animals and plants which contain cells having predetermined modifications of a target DNA sequence in the genome of the organism.
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Publication:7/16
Publication No:US 2008/0295192 A1
Title:SELF-INDUCED DELETION OF DNA
Publication Type:Patent Application Publication
Publication Date:Nov. 27, 2008
Filing Date:June 7, 2007
Inventors:Kirk R. Thomas, Kenneth E. Bernstein, Michaeline Bunting, Joy Greer, Mario Capecchi,
Assignee:
Abstract:The present invention is directed to a method for deleting DNA sequences in a tissue specific manner. In one embodiment, DNA sequences are specifically deleted in germline tissue. In a second embodiment, DNA sequences are specifically deleted in desired somatic tissue. The present invention is further directed to a nucleic acid molecule for use in the method. More specifically, a nucleic acid molecule is provide by the present invention which comprises (a) a recombinase site, (b) a tissue-specific promoter, (c) a recombinase gene, (d) a foreign DNA, and (e) a recombinase site. The nucleic acid molecule may further comprise a gene which is desired to be incorporated into and expressed in a transgenic organism. The method can be used in both plants and animals, and has many applications as described herein.
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Publication:8/16
Publication No:US 5,487,992 A
Title:Cells And Non-human Organisms Containing Predetermined Genomic Modifications And Positive-negative Selection Methods And Vectors For Making Same
Publication Type:United States Utility Patent
Publication Date:Jan. 30, 1996
Filing Date:June 28, 1993
Inventors:Mario R. Capecchi; Kirk R. Thomas
Assignee:University of Utah Research Foundation
Abstract:Positive-negative selector (PNS) vectors are provided for modifying a target DNA sequence contained in the genome of a target cell capable of homologous recombination. The vector comprises a first DNA sequence which contains at least one sequence portion which is substantially homologous to a portion of a first region of a target DNA sequence. The vector also includes a second DNA sequence containing at least one sequence portion which is substantially homologous to another portion of a second region of a target DNA sequence. A third DNA sequence is positioned between the first and second DNA sequences and encodes a positive selection marker which when expressed is functional in the target cell in which the vector is used. A fourth DNA sequence encoding a negative selection marker, also functional in the target cell, is positioned 5' to the first or 3' to the second DNA sequence and is substantially incapable of homologous recombination with the target DNA sequence. The invention also includes transformed cells containing at least one predetermined modification of a target DNA sequence contained in the genome of the cell. In addition, the invention includes organisms such as non-human transgenic animals and plants which contain cells having predetermined modifications of a target DNA sequence in the genome of the organism.
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Publication:9/16
Publication No:US 5627059 A
Title:Cells and non-human organisms containing predetermined genomic modifications and positive-negative selection methods and vectors for making same
Publication Type:Grant
Publication Date:May 06, 1997
Filing Date:June 05, 1995
Inventors:Mario R. Capecchi; Kirk R. Thomas
University of Utah
Abstract:Positive-negative selector (PNS) vectors are provided for modifying a target DNA sequence contained in the genome of a target cell capable of homologous recombination. The vector comprises a first DNA sequence which contains at least one sequence portion which is substantially homologous to a portion of a first region of a target DNA sequence. The vector also includes a second DNA sequence containing at least one sequence portion which is substantially homologous to another portion of a second region of a target DNA sequence. A third DNA sequence is positioned between the first and second DNA sequences and encodes a positive selection marker which when expressed is functional in the target cell in which the vector is used. A fourth DNA sequence encoding a negative selection marker, also functional in the target cell, is positioned 5' to the first or 3' to the second DNA sequence and is substantially incapable of homologous recombination with the target DNA sequence. The invention also includes transformed cells containing at least one predetermined modification of a target DNA sequence contained in the genome of the cell. In addition, the invention includes organisms such as non-human transgenic animals and plants which contain cells having predetermined modifications of a target DNA sequence in the genome of the organism.
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Publication:10/16
Publication No:US 5,631,153 A
Title:Cells and non-human organisms containing predetermined genomic modifications and positive-negative selection methods and vectors for making same
Publication Type:United States Utility Patent
Publication Date:May 20, 1997
Filing Date:June 5, 1995
Inventors:Mario R. Capecchi; Kirk R. Thomas
Assignee:University of Utah
Abstract:Positive-negative selector (PNS) vectors are provided for modifying a target DNA sequence contained in the genome of a target cell capable of homologous recombination. The vector comprises a first DNA sequence which contains at least one sequence portion which is substantially homologous to a portion of a first region of a target DNA sequence. The vector also includes a second DNA sequence containing at least one sequence portion which is substantially homologous to another portion of a second region of a target DNA sequence. A third DNA sequence is positioned between the first and second DNA sequences and encodes a positive selection marker which when expressed is functional in the target cell in which the vector is used. A fourth DNA sequence encoding a negative selection marker, also functional in the target cell, is positioned 5' to the first or 3' to the second DNA sequence and is substantially incapable of homologous recombination with the target DNA sequence. The invention also includes transformed cells containing at least one predetermined modification of a target DNA sequence contained in the genome of the cell. In addition, the invention includes organisms such as non-human transgenic animals and plants which contain cells having predetermined modifications of a target DNA sequence in the genome of the organism.
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Publication:11/16
Publication No:US 6,204,061 B1
Title:Cells and non-human organisms containing predetermined genomic modifications and positive-negative selection methods and vectors for making same
Publication Type:Grant
Publication Date:Mar. 20, 2001
Filing Date:Jan. 9, 1997
Inventors:Mario R. Capecchi; Kirk R. Thomas
Assignee:University of Utah Research Foundation
Abstract:Positive-negative selector (PNS) vectors are provided for modifying a target DNA sequence contained in the genome of a target cell capable of homologous recombination. The vector comprises a first DNA sequence which contains at least one sequence portion which is substantially homologous to a portion of a first region of a target DNA sequence. The vector also includes a second DNA sequence containing at least one sequence portion which is substantially homologous to another portion of a second region of a target DNA sequence. A third DNA sequence is positioned between the first and second DNA sequences and encodes a positive selection marker which when expressed is functional in the target cell in which the vector is used. A fourth DNA sequence encoding a negative selection marker, also functional in the target cell, is positioned 5' to the first or 3' to the second DNA sequence and is substantially incapable of homologous recombination with the target DNA sequence. The invention also includes transformed cells containing at least one predetermined modification of a target DNA sequence contained in the genome of the cell. In addition, the invention includes organisms such as non-human transgenic animals and plants which contain cells having predetermined modifications of a target DNA sequence in the genome of the organism.
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Publication:12/16
Publication No:US 6,689,610 B1
Title:Cells and non-human organisms containing predetermined genomic modifications and positive-negative selection methods and vectors for making same
Publication Type:Grant
Publication Date:Feb. 10, 2004
Filing Date:Nov. 28, 1000
Inventors:Mario R. Capecchi; Kirk R. Thomas
Assignee:University of Utah Research Foundation
Abstract:Positive-negative selector (PNS) vectors are provided for modifying a target DNA sequence contained in the genome of a target cell capable of homologous recombination. The vector comprises a first DNA sequence which contains at least one sequence portion which is substantially homologous to a portion of a first region of a target DNA sequence. The vector also includes a second DNA sequence containing at least one sequence portion which is substantially homologous to another portion of a second region of a target DNA sequence. A third DNA sequence is positioned between the first and second DNA sequences and encodes a positive selection marker which when expressed is functional in the target cell in which the vector is used. A fourth DNA sequence encoding a negative selection marker, also functional in the target cell, is positioned 5' to the first or 3' to the second DNA sequence and is substantially incapable of homologous recombination with the target DNA sequence. The invention also includes transformed cells containing at least one predetermined modification of a target DNA sequence contained in the genome of the cell. In addition, the invention includes organisms such as non-human transgenic animals and plants which contain cells having predetermined modifications of a target DNA sequence in the genome of the organism.
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Publication:13/16
Publication No:US 7,439,415 B2
Title:Population of hoxb8 mutants and uses in identifying agents for treating repetitive behaviors
Publication Type:Grant
Publication Date:Oct. 21, 2008
Filing Date:May 31, 2002
Inventors:Joy M. Greer, Mario R. Capecchi
Assignee:
Abstract:This invention provides in vivo and in vitro methods of screening for an agent or a combination of agents that reduces one or more repetitive behaviors, comprising contacting neuronal cells of an animal with a HOXB8 gene mutation with the agent combination of agents to be screened, and determining whether one or more repetitive behaviors of the animal is reduced or whether one or more biochemical correlates of repetitive behaviors is reduced, the reduction in one or more repetitive behaviors or biochemical correlates indicating an agent or combination of agents that reduces repetitive behaviors. The invention also provides method of treating a subject with repetitive behaviors, comprising administering a therapeutically effective dose of the agent or combination of agents identified by the screening method. Further provided is a population of animals with a HOXB8 gene mutation, wherein more than 30% of the animals have excessive grooming behaviors and wherein less than 10% of the animals show skeletal defects.
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Family
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Publication:14/16
Publication No:US 2010/0178696 A1
Title:IN VIVO GENOME-WIDE MUTAGENESIS
Publication Type:Patent Application Publication
Publication Date:July 15, 2010
Filing Date:Feb. 8, 2008
Inventors:Sen Wu; Mario R. Capecchi
Assignee:University of Utah Research Foundation
Abstract:Disclosed herein are compositions and methods for deleting or duplicating DNA in a mammalian genome. Also disclosed are compositions and methods for generating a random genome-wide chromosome rearrangement. Also disclosed are compositions and methods for streamlined construction of gene targeting vectors.
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Publication:15/16
Publication No:US 2950166 A
Title:Animal Model of Synovial Sarcoma
Publication Type:Patent Application Publication
Publication Date:Mar. 10, 2011
Filing Date:Jul. 22, 2008
Inventors:Malay Haldar; Mario R. Capecchi
Assignee:University of Utah Research Foundation
Abstract:Synovial sarcoma is an aggressive soft-tissue malignancy. Disclosed herein is an animal model of synovial sarcoma wherein one or more myogenic cells of the animal express recombinant SYT-SSX fusion polypeptide. Using this model, myoblasts were identified as a source of synovial sarcoma. Remarkably, within the skeletal muscle lineage, while expression of the oncoprotein in immature myoblasts leads to induction of synovial sarcoma with 100% penetrance, its expression in more differentiated cells induces myopathy without tumor induction. In addition, early widespread expression of the disclosed fusion protein disrupts normal embryogenesis, causing lethality.
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Publication:16/16
Publication No:US 8,546,135 B2
Title:In vivo genome-wide mutagenesis
Publication Type:Grant
Publication Date:Oct. 1, 2013
Filing Date:Feb. 8, 2008
Inventors:Sen Wu; Mario R. Capecchi
Assignee:University of Utah Research Foundation
Abstract:Disclosed herein are compositions and methods for deleting or duplicating DNA in a mammalian genome. Also disclosed are compositions and methods for generating a random genome-wide chromosome rearrangement. Also disclosed are compositions and methods for streamlined construction of gene targeting vectors.
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Name: Mario Ramberg Capecchi Ph.D.
Birth: 6 October 1937, Verona, Italy
Institution: University of Utah, Salt Lake City, UT, USA, Howard Hughes Medical Institute
Award: "for their discoveries of principles for introducing specific gene modifications in mice by the use of embryonic stem cells"
Subject: Genetics
Portion of cash: 1/2
National Medal of Science - Biological Sciences 2001
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