Involving General Or Homologous Recombination (e.g., Gene Targeting, Etc.) Patents (Class 435/463)
  • Patent number: 11851663
    Abstract: The invention relates to the production and use of Cas-encoding sequences and vectors comprising these. Aspects of the invention provide products, vectors, delivery vehicles, uses and methods for producing Cas-encoding sequences in bacterial or archaeal cells.
    Type: Grant
    Filed: November 27, 2018
    Date of Patent: December 26, 2023
    Assignee: SNIPR BIOME APS
    Inventors: Virginia Martinez, Ruben Vazquez-Uribe, Adam Takos, Eric Van Der Helm
  • Patent number: 11642375
    Abstract: Genetically modified compositions, such as non-viral vectors and T cells, for treating cancer are disclosed. Also disclosed are the methods of making and using the genetically modified compositions in treating cancer.
    Type: Grant
    Filed: November 6, 2018
    Date of Patent: May 9, 2023
    Assignees: INTIMA BIOSCIENCE, INC., REGENTS OF THE UNIVERSITY OF MINNESOTA, THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES
    Inventors: Branden Moriarity, Beau Webber, Modassir Choudhry, Steven A. Rosenberg, Douglas C. Palmer, Nicholas P. Restifo
  • Patent number: 11464849
    Abstract: The invention relates to recombinant viral vectors for the insertion and expression of foreign genes for use in safe immunizations to protect against a variety of pathogens. The invention also relates to multivalent compositions or vaccine comprising one or more recombinant viral vectors for protection against a variety of pathogens. The present invention relates to methods of making an using said recombinant viral vectors.
    Type: Grant
    Filed: September 10, 2020
    Date of Patent: October 11, 2022
    Assignee: Zoetis Services LLC
    Inventors: Sing Rong, Yugang Luo, Tyler Brown
  • Patent number: 11357217
    Abstract: Mice, tissues, cells, and genetic material are provided that comprise a humanized heavy chain immunoglobulin locus, a humanized light chain locus that expresses a universal light chain, and a gene encoding an ADAM6 or ortholog or homolog or functional fragment thereof. Mice are provided that express humanized heavy chains comprising human variable domains, and that express humanized light chains comprising human variable domains wherein the light chains are derived from no more than one, or no more than two, light chain V and J or rearranged V/J sequences. Fertile male mice that express antibodies with universal light chains and humanized heavy chains are provided. Methods and compositions for making bispecific binding proteins are provided.
    Type: Grant
    Filed: October 2, 2018
    Date of Patent: June 14, 2022
    Assignee: Regeneron Pharmaceuticals, Inc.
    Inventors: John McWhirter, Lynn Macdonald, Sean Stevens, Andrew J. Murphy, Margaret Karow
  • Patent number: 11248240
    Abstract: The present invention relates to a fusion protein comprising a Cas9 domain and a Spo11 domain, as well as the use of this protein to induce targeted meiotic recombinations in a eukaryotic cell.
    Type: Grant
    Filed: January 29, 2016
    Date of Patent: February 15, 2022
    Assignees: MEIOGENIX, INSTITUT CURIE, CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE, SORBONNE UNIVERSITE
    Inventors: Giacomo Bastianelli, Alexandre Serero, Alain Nicolas
  • Patent number: 11071289
    Abstract: The present disclosure relates to an efficient genome editing technique. In one aspect, the technique can greatly improve the efficiency of homologous recombination during intracellular targeting, including gene targeting. Using this technique, genetically modified cell lines, rat, mouse, zebrafish, and fertilized eggs of other species can be quickly and efficiently generated.
    Type: Grant
    Filed: August 13, 2015
    Date of Patent: July 27, 2021
    Assignee: Biocytogen Boston Corp
    Inventor: Yuelei Shen
  • Patent number: 10966411
    Abstract: Described are transgenic, non-human animals comprising a nucleic acid encoding an immunoglobulin light chain, whereby the immunoglobulin light chain is human, human-like, or humanized. The nucleic acid is provided with a means that renders it resistant to DNA rearrangements and/or somatic hypermutations. In one embodiment, the nucleic acid comprises an expression cassette for the expression of a desired molecule in cells during a certain stage of development in cells developing into mature B cells. Further provided is methods for producing an immunoglobulin from the transgenic, non-human animal.
    Type: Grant
    Filed: October 19, 2009
    Date of Patent: April 6, 2021
    Assignee: Merus N.V.
    Inventors: Ton Logtenberg, Mark Throsby, Robert A. Kramer, Rui Daniel Pinto, Cornelis A. de Kruif, Erwin Houtzager
  • Patent number: 10966412
    Abstract: The invention discloses methods for the generation of chimaeric human-non-human antibodies and chimaeric antibody chains, antibodies and antibody chains so produced, and derivatives thereof including fully humanised antibodies; compositions comprising said antibodies, antibody chains and derivatives, as well as cells, non-human mammals and vectors, suitable for use in said methods.
    Type: Grant
    Filed: December 11, 2018
    Date of Patent: April 6, 2021
    Assignee: Kymab Limited
    Inventors: E-Chiang Lee, Jasper Clube, Allan Bradley
  • Patent number: 10881084
    Abstract: The present invention comprises non-human vertebrate cells and non-human mammals having a genome comprising an introduced partially human immunoglobulin region, said introduced region comprising human VH coding sequences and non-coding VH sequences based on the endogenous genome of the non-human mammal.
    Type: Grant
    Filed: July 26, 2011
    Date of Patent: January 5, 2021
    Assignee: TRIANNI, INC
    Inventors: Matthias Wabl, Nigel Killeen
  • Patent number: 10655134
    Abstract: The present invention relates to a method for the production of recombinant expression vectors, a kit adapted to carrying out the method, a vector used in the context of the method, a cell containing such vector and the use of the vector.
    Type: Grant
    Filed: May 9, 2017
    Date of Patent: May 19, 2020
    Assignee: EBERHARD KARLS UNIVERSITAET TUEBINGEN MEDIZINISCHE FAKULTAETGESCHWISTER-SCHOLL-PLATZ
    Inventors: Ralf Amann, Hans-Joachim Rziha
  • Patent number: 10582702
    Abstract: Non-human animals, and methods and compositions for making and using the same, are provided, wherein said non-human animals comprise a humanization of an Angiopoietin-like protein 8 (ANGPTL8) gene. Said non-human animals may be described, in some embodiments, as having a genetic modification to an endogenous ANGPTL8 locus so that said non-human animals express a human ANGPTL8 polypeptide.
    Type: Grant
    Filed: February 3, 2017
    Date of Patent: March 10, 2020
    Assignee: REGENERON PHARMACEUTICALS, INC.
    Inventors: Viktoria Gusarova, Andrew J. Murphy, Jesper Gromada, Dayong Guo
  • Patent number: 10542735
    Abstract: Mice, embryos, cells, and tissues having a restricted immunoglobulin heavy chain locus and an ectopic sequence encoding one or more ADAM6 proteins are provided. In various embodiments, mice are described that have humanized endogenous immunoglobulin heavy chain loci and are capable of expressing an ADAM6 protein or ortholog or homolog or functional fragment thereof that is functional in a male mouse. Mice, embryos, cells, and tissues having an immunoglobulin heavy chain locus characterized by a single human VH gene segment, a plurality of human DH gene segments and a plurality of human JH gene segments and capable expressing an ADAM6 protein or ortholog or homolog or functional fragment thereof are also provided.
    Type: Grant
    Filed: December 17, 2018
    Date of Patent: January 28, 2020
    Assignee: Regerneron Pharmaceuticals, Inc.
    Inventors: Lynn Macdonald, Naxin Tu, Sean Stevens, Andrew J. Murphy, Margaret Karow
  • Patent number: 10370680
    Abstract: Disclosed herein are methods and compositions for targeted, nuclease-mediated insertion of transgene sequences into the genome of a cell.
    Type: Grant
    Filed: February 24, 2015
    Date of Patent: August 6, 2019
    Assignee: Sangamo Therapeutics, Inc.
    Inventors: Michael C. Holmes, Thomas Wechsler
  • Patent number: 10314297
    Abstract: The present disclosure relates to an efficient genome editing technique. In one aspect, the technique can greatly improve the efficiency of homologous recombination during intracellular targeting, including gene targeting. Using this technique, genetically modified cell lines, rat, mouse, zebrafish, and fertilized eggs of other species can be quickly and efficiently generated.
    Type: Grant
    Filed: September 11, 2017
    Date of Patent: June 11, 2019
    Assignee: Biocytogen Boston Corp
    Inventor: Yuelei Shen
  • Patent number: 10246509
    Abstract: Mice having a restricted immunoglobulin heavy chain locus are provided, wherein the locus is characterized by a single polymorphic human VH gene segment, a plurality of human DH gene segments and a plurality of JH gene segments. Methods for making antibody sequences that bind an antigen (e.g., a viral antigen) are provided, comprising immunizing a mouse with an antigen of interest, wherein the mouse comprises a single human VH gene segment, a plurality of human DH gene segments and a plurality of JH gene segments, at the endogenous immunoglobulin heavy chain locus.
    Type: Grant
    Filed: October 17, 2012
    Date of Patent: April 2, 2019
    Assignee: Regeneron Pharmaceuticals, Inc.
    Inventors: Lynn Macdonald, John McWhirter, Cagan Gurer, Karolina A. Hosiawa, Andrew J. Murphy
  • Patent number: 10238093
    Abstract: Mice, embryos, cells, and tissues having a restricted immunoglobulin heavy chain locus and an ectopic sequence encoding one or more ADAM6 proteins are provided. In various embodiments, mice are described that have humanized endogenous immunoglobulin heavy chain loci and are capable of expressing an ADAM6 protein or ortholog or homolog or functional fragment thereof that is functional in a male mouse. Mice, embryos, cells, and tissues having an immunoglobulin heavy chain locus characterized by a single human VH gene segment, a plurality of human DH gene segments and a plurality of human JH gene segments and capable expressing an ADAM6 protein or ortholog or homolog or functional fragment thereof are also provided.
    Type: Grant
    Filed: March 7, 2013
    Date of Patent: March 26, 2019
    Assignee: Regeneron Pharmaceuticals, Inc.
    Inventors: Lynn Macdonald, John McWhirter, Sean Stevens, Andrew J. Murphy
  • Patent number: 10143186
    Abstract: A genetically modified mouse is provided, wherein the mouse is incapable of rearranging and expressing an endogenous mouse immunoglobulin light chain variable sequence, wherein the mouse expresses only one or two human light chain variable domains encoded by human immunoglobulin sequences operably linked to the mouse kappa (?) constant gene at the endogenous mouse ? locus, wherein the mouse expresses a reverse chimeric antibody having a light chain variable domain derived from one of only two human light chain variable region gene segments and a mouse ? constant domain, and a human heavy chain variable domain and a mouse heavy chain constant domain, from an endogenous mouse heavy chain locus. Bispecific epitope-binding proteins that are fully human are provided, comprising two different heavy chains that associate with an identical light chain that comprises a variable domain derived from one of two different human light chain variable region gene segments.
    Type: Grant
    Filed: February 8, 2011
    Date of Patent: December 4, 2018
    Assignee: Regeneron Pharmaceuticals, Inc.
    Inventors: John McWhirter, Lynn Macdonald, Sean Stevens, David R. Buckler, Andrew J. Murphy
  • Patent number: 10130081
    Abstract: Mice, tissues, cells, and genetic material are provided that comprise a humanized heavy chain immunoglobulin locus, a humanized light chain locus that expresses a universal light chain, and a gene encoding an ADAM6 or ortholog or homolog or functional fragment thereof. Mice are provided that express humanized heavy chains comprising human variable domains, and that express humanized light chains comprising human variable domains wherein the light chains are derived from no more than one, or no more than two, light chain V and J or rearranged V/J sequences. Fertile male mice that express antibodies with universal light chains and humanized heavy chains are provided. Methods and compositions for making bispecific binding proteins are provided.
    Type: Grant
    Filed: August 3, 2012
    Date of Patent: November 20, 2018
    Assignee: Regeneron Pharmaceuticals, Inc.
    Inventors: John McWhirter, Lynn MacDonald, Sean Stevens, Andrew J. Murphy, Margaret Karow
  • Patent number: 10072066
    Abstract: Methods and compositions for treatment of a beta thalessemia are provided.
    Type: Grant
    Filed: February 2, 2015
    Date of Patent: September 11, 2018
    Assignee: Sangamo Therapeutics, Inc.
    Inventors: Pei-Qi Liu, Andreas Reik, Lei Zhang
  • Patent number: 9955676
    Abstract: The present invention provides an in vivo platform for identifying and determining therapeutic or prophylactic activity of test compounds in delay-type hypersensitivity (DTH) and other inflammatory or cancerous diseases mediated by activation of IKK-?C46A mutants. The in vivo platform of the present invention is a non-human transgenic mammal, e.g., a mouse model, with a site directed mutagenesis at a cysteine residue replaced by alanine in IKK-? protein kinase. The site directed mutagenesis is introduced by a specially designed targeting vector containing a transversion in exon 3 of the Ikbkb genes encoding the IKK-?. The present invention also provides methods for generating the transgenic mammal and for determining and identifying compounds that can inhibit activation of IKK-?C46A mutants.
    Type: Grant
    Filed: February 11, 2015
    Date of Patent: May 1, 2018
    Assignee: Macau University of Science and Technology
    Inventors: Liang Liu, Ting Li, Kam Wai Wong, Zhihong Jiang, Hua Zhou
  • Patent number: 9822370
    Abstract: Disclosed herein are methods, compositions, and kits for high efficiency, site-specific genomic editing of cells.
    Type: Grant
    Filed: September 12, 2014
    Date of Patent: November 21, 2017
    Assignees: President and Fellows of Harvard College, The Children's Medical Center Corporation
    Inventors: Kiran Musunuru, Chad A. Cowan, Derrick J. Rossi
  • Patent number: 9516868
    Abstract: Genetically modified mice and methods for making an using them are provided, wherein the mice comprise a replacement of all or substantially all immunoglobulin heavy chain V gene segments, D gene segments, and J gene segments with at least one light chain V gene segment and at least one light chain J gene segment. Mice that make binding proteins that comprise a light chain variable domain operably linked to a heavy chain constant region are provided. Binding proteins that contain an immunoglobulin light chain variable domain, including a somatically hypermutated light chain variable domain, fused with a heavy chain constant region, are provided. Modified cells, embryos, and mice that encode sequences for making the binding proteins are provided.
    Type: Grant
    Filed: August 2, 2011
    Date of Patent: December 13, 2016
    Assignee: Regeneron Pharmaceuticals, Inc.
    Inventors: Lynn Macdonald, Sean Stevens, Cagan Gurer, Karolina A. Hosiawa, Andrew J. Murphy
  • Patent number: 9255250
    Abstract: Cells and methods of using these cells for expressing a transgene expressing a protein that is aberrantly expressed in a metabolic disorders from a safe harbor locus.
    Type: Grant
    Filed: December 4, 2013
    Date of Patent: February 9, 2016
    Assignees: Sangamo BioScience, Inc., The Children's Hospital of Philadelphia
    Inventors: Philip D. Gregory, Katherine A. High
  • Patent number: 9217146
    Abstract: The present invention is based, at least in part, upon discovery of a process for identifying phase changing peptides. Such phase changing peptides are capable of enhancing in vitro and in vivo delivery of oligonucleotides (e.g., dsRNAs) in lipidic, vesicular, micellar and/or naked oligonucleotide formulations.
    Type: Grant
    Filed: December 13, 2013
    Date of Patent: December 22, 2015
    Assignee: Dicerna Pharmaceuticals, Inc.
    Inventors: Bob Dale Brown, Sujit Kumar Basu
  • Patent number: 9217160
    Abstract: Methods of assembling modified adenoviruses, libraries of adenoviral gene modules and compositions thereof are provided herein.
    Type: Grant
    Filed: February 15, 2013
    Date of Patent: December 22, 2015
    Assignee: Salk Institute for Biological Studies
    Inventors: Clodagh O'Shea, Colin Powers
  • Patent number: 9163092
    Abstract: Genetically modified mice are provided that express human ? variable (hV?) sequences, including mice that express hV? sequences from an endogenous mouse ? light chain locus, mice that express hV? sequences from an endogenous mouse ? light chain locus, and mice that express hV? sequences from a transgene or an episome wherein the hV? sequence is linked to a mouse constant sequence. Mice are provided that are a source of somatically mutated human ? variable sequences useful for making antigen-binding proteins. Compositions and methods for making antigen-binding proteins that comprise human ? variable sequences, including human antibodies, are provided.
    Type: Grant
    Filed: May 18, 2015
    Date of Patent: October 20, 2015
    Assignee: Regeneron Pharmaceuticals, Inc.
    Inventors: Lynn Macdonald, Sean Stevens, Cagan Gurer, Andrew J. Murphy, Karolina A. Meagher
  • Patent number: 9150662
    Abstract: Genetically modified mice are provided that express human ? variable (hV?) sequences, including mice that express hV? sequences from an endogenous mouse ? light chain locus, mice that express hV? sequences from an endogenous mouse ? light chain locus, and mice that express hV? sequences from a transgene or an episome wherein the hV? sequence is linked to a mouse constant sequence. Mice are provided that are a source of somatically mutated human ? variable sequences useful for making antigen-binding proteins. Compositions and methods for making antigen-binding proteins that comprise human ? variable sequences, including human antibodies, are provided.
    Type: Grant
    Filed: May 18, 2015
    Date of Patent: October 6, 2015
    Assignee: Regeneron Pharmaceuticals, Inc.
    Inventors: Lynn Macdonald, Sean Stevens, Cagan Gurer, Andrew J. Murphy, Karolina A. Meagher
  • Patent number: 9133485
    Abstract: The invention lies in the field of production of recombinant gene products in eukaryotic cells. The invention refers to methods and materials for the fast and reproducible generation of production cells lines suitable for large scale production of recombinant gene products. The invention encompasses specific vector systems, genetic engineered host-cells and methods of use.
    Type: Grant
    Filed: March 27, 2009
    Date of Patent: September 15, 2015
    Assignee: Celonic AG
    Inventors: Andreas Herrmann, Harry Abts, Benedikt Greulich
  • Patent number: 9066502
    Abstract: Genetically modified mice are provided that express human ? variable (hV?) sequences, including mice that express hV? sequences from an endogenous mouse ? light chain locus, mice that express hV? sequences from an endogenous mouse ? light chain locus, and mice that express hV? sequences from a transgene or an episome wherein the hV? sequence is linked to a mouse constant sequence. Mice are provided that are a source of somatically mutated human ? variable sequences useful for making antigen-binding proteins. Compositions and methods for making antigen-binding proteins that comprise human ? variable sequences, including human antibodies, are provided.
    Type: Grant
    Filed: December 18, 2013
    Date of Patent: June 30, 2015
    Assignee: Regeneron Pharmaceuticals, Inc.
    Inventors: Lynn Macdonald, Sean Stevens, Cagan Gurer, Andrew J. Murphy, Karolina A. Meagher
  • Patent number: 9057057
    Abstract: Disclosed are methods of making and using engineered FokI cleavage domain variants. Also disclosed are methods, compositions and fusion proteins containing obligate heterodimers of engineered FokI cleavage domain variants and DNA binding domains, such as zinc finger protein (ZFP) domains and transcription activator-like effector (TALE) domains.
    Type: Grant
    Filed: July 27, 2011
    Date of Patent: June 16, 2015
    Assignees: THE JOHNS HOPKINS UNIVERSITY, PONDICHERRY BIOTECH PRIVATE LIMITED (PBPL)
    Inventors: Srinivasan Chandrasegaran, Sivaprakash Ramalingam, Karthikeyan Kandavelou
  • Publication number: 20150135345
    Abstract: Rationally-designed LAGLIDADG meganucleases and methods of making such meganucleases are provided. In addition, methods are provided for using the meganucleases to generate recombinant cells and organisms having a desired DNA sequence inserted into a limited number of loci within the genome, as well as methods of gene therapy, for treatment of pathogenic infections, and for in vitro applications in diagnostics and research.
    Type: Application
    Filed: August 19, 2014
    Publication date: May 14, 2015
    Inventors: James Jefferson SMITH, Derek JANTZ, Homme W. HELLINGA
  • Patent number: 9018011
    Abstract: Regulatory elements, specifically insulators and transgene constructs containing insulator nucleic acid sequences, are disclosed herein. Methods of using insulators and transgene constructs including insulators to inhibit, delay, or prevent gene silencing are also disclosed herein.
    Type: Grant
    Filed: February 15, 2008
    Date of Patent: April 28, 2015
    Assignee: The United States as represented by the Secretary of the Department of Health and Human Services
    Inventors: Jung-Hyun Kim, Vladimir L. Larionov, Tom Ebersole
  • Patent number: 9005973
    Abstract: Disclosed herein are donor molecules comprising single-stranded complementary regions flanking one or more sequences of interest. The donor molecules and/or compositions comprising these molecules can be used in methods for targeted integration of an exogenous sequence into a specified region of interest in the genome of a cell.
    Type: Grant
    Filed: July 8, 2011
    Date of Patent: April 14, 2015
    Assignee: Sangamo BioSciences, Inc.
    Inventors: Gregory J. Cost, Dmitry M. Guschin, Fyodor Urnov
  • Patent number: 9005935
    Abstract: The present invention provides new compositions for transposase-mediated fragmenting and tagging DNA targets. The invention relates to the surprising discovery that use of manganese ions (Mn2+) in transposase reactions improves the transposase reaction. It also relates to the surprising discovery that Mg2+ ions can be used in a transposase reaction with wild-type and/or engineered transposases at levels much higher than previously thought. The invention provides for the use of naturally-occurring transposases in in vitro reactions, as well as improved schemes for cleaving, tagging, and amplifying target DNA.
    Type: Grant
    Filed: May 11, 2012
    Date of Patent: April 14, 2015
    Assignee: Agilent Technologies, Inc.
    Inventor: Alexander S. Belyaev
  • Patent number: 8980579
    Abstract: Provided herein are methods for stable integration and/or expression of one or more recombinant polynucleotides in a host cell. The recombinant polynucleotides are typically integrated into the host genome at some native chromosomal integration sites. The integration can be mediated by homologous recombination or by using a hybrid recombinase targeting the specific chromosomal locations. The native chromosomal integration sites in the host cells, which support stable integration and strong transcription activities of foreign genes, are present within or adjacent to specific genes in the CHO genome, the ankyrin 2 gene (Ank2), cleavage and polydenylation specific factor 4 gene (Cpsf4), C-Mos gene, and Nephrocystin-1/Mal gene. Also provided are methods and nucleic acid molecules for inserting site-specific recombination sequences (chromosomal landing pads) into these specific chromosomal locations, engineered host cells containing chromosomal landing pads, methods and compositions (e.g., kits) therefore.
    Type: Grant
    Filed: April 5, 2012
    Date of Patent: March 17, 2015
    Assignee: The Scripps Research Institute
    Inventors: Vincent P. Mauro, Wei Zhou, Bruce Cunningham, Gerald M. Edelman
  • Publication number: 20150047062
    Abstract: Genetically modified non-human animals are provided that exhibit a functional lack of one or more lncRNAs. Methods and compositions for disrupting, deleting, and/or replacing lncRNA-encoding sequences are provided. Genetically modified mice that age prematurely are provided. Also provided are cells, tissues and embryos that are genetically modified to comprise a loss-of-function of one or more lncRNAs.
    Type: Application
    Filed: August 7, 2014
    Publication date: February 12, 2015
    Inventors: Ka-Man Venus Lai, Guochun Gong, John Rinn, David Frendewey, David M. Valenzuela
  • Patent number: 8945927
    Abstract: The present invention relates to a new class of cationic polymers that self-assemble with a pH-sensitive dissolution switch, and their uses to deliver molecules of interest to a cell. The present invention also relates to compositions comprising said cationic polymers non-covalently associated with a molecule of interest, in particular with a siRNA.
    Type: Grant
    Filed: March 29, 2011
    Date of Patent: February 3, 2015
    Assignees: Universite de Strasbourg, Centre National de la Recherche Scientifique
    Inventors: Guy Zuber, Benoit Frisch, Gaelle Creusat, Jean-Sebastien Thomann
  • Patent number: 8936936
    Abstract: Disclosed herein are methods and compositions for targeted integration of one or more copies of a sequence of interest using zinc finger nucleases (ZFNs) comprising a zinc finger protein and a cleavage domain or cleavage half-domain and integrase defective lentiviral donor constructs.
    Type: Grant
    Filed: October 23, 2008
    Date of Patent: January 20, 2015
    Assignees: Sangamo BioSciences, Inc., Ospedale San Raffaele S.R.L.
    Inventors: Michael C. Holmes, Shuyuan Yao, Luigi Naldini, Angelo Leone Lombardo
  • Patent number: 8932860
    Abstract: The invention provides methods and nucleic acid constructs that may be used to modify a nucleic acid of interest at a target locus within the genome of a host. In some aspects, the invention contemplates producing in vivo a gene targeting substrate (GTS), which may be comprised of both DNA and RNA components. The gene targeting substrate may comprise a gene targeting nucleotide sequence (GTNS), which is homologous to the target locus, but comprises a sequence modification compared to the target locus. The gene targeting substrate may be produced by reverse transcription of a gene targeting message RNA (gtmRNA). The gene targeting message RNA may be folded for self-priming for reverse transcription by a reverse transcriptase. The gene targeting message RNA may in turn be the product of transcription of a gene targeting construct (GTC) encoding the gene targeting message RNA.
    Type: Grant
    Filed: August 22, 2008
    Date of Patent: January 13, 2015
    Assignee: Her Majesty in Right of Canada as Represented by the Minister of Agriculture and Agri-Food Canada
    Inventors: Kevin L. Rozwadowski, Derek J. Lydiate
  • Publication number: 20140377870
    Abstract: The present invention provides reagents and methods for improved homologous recombination.
    Type: Application
    Filed: August 29, 2014
    Publication date: December 25, 2014
    Applicant: Arizona Board of Regents, a body corporate of the State of Arizona, acting for and on behalf of Ariz
    Inventors: Bertram JACOBS, Stacy White, Kip Conwell, Jeffrey Langland, James Jancovich, Karen Kibler
  • Publication number: 20140369980
    Abstract: Disclosed herein are methods and compositions for targeted cleavage of a genomic sequence, targeted alteration of a genomic sequence, and targeted recombination between a genomic region and an exogenous polynucleotide homologous to the genomic region. The compositions include fusion proteins comprising a cleavage domain (or cleavage half-domain) and an engineered zinc finger domain and polynucleotides encoding same. Methods for targeted cleavage include introduction of such fusion proteins, or polynucleotides encoding same, into a cell. Methods for targeted recombination additionally include introduction of an exogenous polynucleotide homologous to a genomic region into cells comprising the disclosed fusion proteins.
    Type: Application
    Filed: July 31, 2014
    Publication date: December 18, 2014
    Inventors: Michael C. Holmes, Fyodor Urnov
  • Publication number: 20140356956
    Abstract: Methods of modulating expression of a target nucleic acid in a cell are provided including introducing into the cell a first foreign nucleic acid encoding one or more RNAs complementary to DNA, wherein the DNA includes the target nucleic acid, introducing into the cell a second foreign nucleic acid encoding a nuclease-null Cas9 protein that binds to the DNA and is guided by the one or more RNAs, introducing into the cell a third foreign nucleic acid encoding a transcriptional regulator protein or domain, wherein the one or more RNAs, the nuclease-null Cas9 protein, and the transcriptional regulator protein or domain are expressed, wherein the one or more RNAs, the nuclease-null Cas9 protein and the transcriptional regulator protein or domain co-localize to the DNA and wherein the transcriptional regulator protein or domain regulates expression of the target nucleic acid.
    Type: Application
    Filed: June 30, 2014
    Publication date: December 4, 2014
    Inventors: George M. CHURCH, Prashant G. MALI, Kevin M. ESVELT
  • Publication number: 20140335621
    Abstract: Provided is a gene targeting vector that enables highly efficient gene targeting. The gene targeting vector has a structure comprising a positive selection marker flanked by a DNA homologous to a 5?-upstream region of a target site and a DNA homologous to a 3?-downstream region of the target site, wherein a splice acceptor site and a DNA sequence allowing for bicistronic expression are added 5?-upstream of the positive selection marker, and another splice acceptor site is also added 5?-upstream of the DNA homologous to the 5?-upstream region of the target site.
    Type: Application
    Filed: December 12, 2012
    Publication date: November 13, 2014
    Inventor: Noritaka Adachi
  • Patent number: 8871516
    Abstract: The present invention is directed to a method for preparing an expression vector encoding a tailored recombinase, wherein said tailored recombinase recombines asymmetric target sites within the LTR of proviral DNA of a retrovirus inserted into the genome of a host cell and is useful as means for excising the provirus from the genome of the host cell. The present invention further relates to an in vitro-method of optimising the treatment of a retroviral infection of a subject and to the use of tailored recombinases for the preparation of pharmaceutical compositions for reducing the viral load in a subjected infected by a retrovirus.
    Type: Grant
    Filed: January 3, 2008
    Date of Patent: October 28, 2014
    Assignees: Technische Universität Dresden, Max-Planck-Gesellschaft zur Förderung der Wissenschaften E.V., Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie an der Universität Hamburg
    Inventors: Joachim Hauber, Frank Buchholz, Ilona Hauber, Francis A Stewart, Indrani Sarkar
  • Publication number: 20140315257
    Abstract: Provided is a gene targeting vector capable of highly efficient gene targeting. A gene targeting vector in which a DNA sequence allowing for bicistronic expression is present 5? upstream of a selection marker. A method for producing a gene targeting vector, comprising linking a DNA fragment homologous to a 5? upstream region of a target site, a selection marker having a DNA sequence allowing for bicistronic expression present 5? upstream thereof, and a DNA fragment homologous to a 3? downstream region of the target site.
    Type: Application
    Filed: May 24, 2012
    Publication date: October 23, 2014
    Applicant: PUBLIC UNIVERSITY CORPORATION YOKOHAMA CITY UNIVERSITY
    Inventor: Noritaka Adachi
  • Patent number: 8859275
    Abstract: The invention relates to nucleic acid modifications for a directed expression modulation by the targeted insertion or removal of CpG dinucleotides. The invention also relates to modified nucleic acids and expression vectors.
    Type: Grant
    Filed: August 3, 2005
    Date of Patent: October 14, 2014
    Assignee: GeneArt AG
    Inventors: Frank Notka, Marcus Graf, Doris Leikam, Ralf Wagner, David Raab
  • Publication number: 20140296093
    Abstract: The present invention provides compositions and methods for recombinational cloning. The compositions include vectors having multiple recombination sites with unique specificity. The methods permit the simultaneous cloning of two or more different nucleic acid molecules. In some embodiments the molecules are fused together while in other embodiments the molecules are inserted into distinct sites in a vector. The invention also generally provides for linking or joining through recombination a number of molecules and/or compounds (e.g., chemical compounds, drugs, proteins or peptides, lipids, nucleic acids, carbohydrates, etc.) which may be the same or different. Such molecules and/or compounds or combinations of such molecules and/or compounds can also be bound through recombination to various structures or supports according to the invention.
    Type: Application
    Filed: February 28, 2014
    Publication date: October 2, 2014
    Applicant: LIFE TECHNOLOGIES CORPORATION
    Inventors: Michael BRASCH, Devon Byrd, David Cheo, James Hartley, Gary Temple
  • Patent number: 8846387
    Abstract: This invention provides methods for obtaining targeted gene modification in vertebrate cells using parvoviral vectors, including adeno-associated virus (AAV). The parvoviral vectors used in the methods of the invention are capable of targeting a specific genetic modification to a preselected target locus in a cellular genome by homologous pairing.
    Type: Grant
    Filed: May 24, 2011
    Date of Patent: September 30, 2014
    Assignee: The University of Washington
    Inventors: David W. Russell, Roli K. Hirata
  • Patent number: 8846402
    Abstract: A method for engineering and utilizing large DNA vectors to target, via homologous recombination, and modify, in any desirable fashion, endogenous genes and chromosomal loci in eukaryotic cells. These large DNA targeting vectors for eukaryotic cells, termed LTVECs, are derived from fragments of cloned genomic DNA larger than those typically used by other approaches intended to perform homologous targeting in eukaryotic cells. Also provided is a rapid and convenient method of detecting eukaryotic cells in which the LTVEC has correctly targeted and modified the desired endogenous gene(s) or chromosomal locus (loci) as well as the use of these cells to generate organisms bearing the genetic modification.
    Type: Grant
    Filed: December 19, 2012
    Date of Patent: September 30, 2014
    Assignee: Regeneron Pharmaceuticals, Inc.
    Inventors: Aris N. Economides, Andrew J. Murphy, David M. Valenzuela, David Frendewey, George D. Yancopoulos
  • Patent number: 8790896
    Abstract: The present invention relates to a method for increasing the expression of a protein in cells, preferably in eukaryotic cells, by reducing the number of RNase L cleavage sites in the coding and/or non-coding region of the nucleic acid sequence of said protein. Furthermore, it relates to nucleic acid sequences exhibiting a reduced number of RNase L cleavage sites as well as to the proteins translated from such sequences.
    Type: Grant
    Filed: January 19, 2010
    Date of Patent: July 29, 2014
    Assignees: King Faisal Specialist Hospital & Research Centre, Terramark Markencreation GmbH
    Inventor: Khalid S. Khabar