Abstract: In methods for screening treatments for, and treatment of, neurodegenerative diseases, aggregation in neurons of NACP/?-synuclein is measured and expression of a non-amyloidogenic protein is stimulated in order to reduce the level aggregration. For purposes of screening agents for treatment of neurodegenerative disease, oxidative stress in the neuronal cells is stimulated by introducing a mixture of metal-ions and hydrogen peroxide. Examples of appropriate metals include iron, aluminum, and copper. After introduction of the agent under evaluation for stimulation of expression of non-amyloidogenic protein, the effectiveness is measured by testing for a decrease in the level of aggregation of NACP/?-synuclein. In an exemplary embodiment, the non-amyloidogenic protein is ?-synuclein. The aggregation of NACP/?-synuclein is dependent upon the concentration of metal ions in the neuronal cells.
Type:
Grant
Filed:
May 24, 2004
Date of Patent:
December 2, 2008
Assignee:
The Regents of the University of California
Inventors:
Eliezer Masliah, Makoto Hashimoto, Edward Rockenstein, Lennart Mucke
Abstract: The present invention relates to transcription control elements derived from mouse and human genes associated with cytochrome expression, e.g., Cyp3A11 and CYP3A4, respectively. Isolated polynucleotides, expression cassettes, vectors, recombinant cells, and transgenic animals, may comprise such transcription control elements as described herein.
Type:
Grant
Filed:
April 11, 2002
Date of Patent:
November 11, 2008
Assignee:
Xenogen Corporation
Inventors:
Weisheng Zhang, Pamela Contag, Anthony Purchio, Sandy Hashima, Shirley Ma, Kevin Nawotka
Abstract: The present invention relates to germ line and somatic cells comprising a mutant p27kip1 protein lacking a Cdk2 phosphorylation site. Also provided are transgenic animals and methods of making such transgenic animals which have increased size and/or growth rate.
Abstract: The present invention provides methods of screening an agent for activity using teleosts. Methods of screening an agent for angiogenesis activity, toxic activity and an effect cell death activity in teleosts are provided.
Type:
Grant
Filed:
November 15, 2005
Date of Patent:
October 14, 2008
Assignee:
Phylonix Pharmaceuticals, Inc.
Inventors:
George N. Serbedzija, Carlos Semino, Deanna Frost
Abstract: Novel GPCR GAVE10 polypeptides, proteins and nucleic acid molecules are provided. GAVE10, recombinant expression vectors, host cells incorporating GAVE10 expression vectors and non-human transgenic animals into which a GAVE10 gene has been introduced or disrupted are taught. Diagnostic, screening and therapeutic methods utilizing compositions of the invention also are provided.
Type:
Grant
Filed:
September 30, 2002
Date of Patent:
October 7, 2008
Assignee:
Aventis Pharmaceuticals Inc.
Inventors:
Haifeng Eishingdrelo, Mohamad Ali Ardati, Jidong Cai
Abstract: The present invention provides vaccines and methods for making the vaccines that actively or passively protect an equid or other animal against Sarcocystis neurona. In particular, the present invention provides vaccines that provide active immunity which comprise a polypeptide or DNA vaccine that contains or expresses at least one epitope of an antigen that has an amino acid sequence substantially similar to a unique 16 (±4) kDa antigen and/or 30 (±4) kDa antigen of Sarcocystis neurona. The present invention further provides a vaccine that provides passive immunity to Sarcocystis neurona comprising polyclonal or monoclonal antibodies against at least one epitope of an antigen substantially similar to a unique 16 (±4) kDa antigen and/or 30 (±4) kDa antigen of Sarcocystis neurona.
Type:
Grant
Filed:
February 24, 2000
Date of Patent:
September 2, 2008
Assignee:
Board of Trustees of Michigan State University
Inventors:
Linda S. Mansfield, Mary G. Rossano, Alice J. Murphy, Ruth A. Vrable
Abstract: This disclosure provides an improved system for culturing human pluripotent stem cells. Traditionally, pluripotent stem cells are cultured on a layer of feeder cells (such as mouse embryonic fibroblasts) to prevent them from differentiating. In the system described here, the role of feeder cells is replaced by components added to the culture environment that support rapid proliferation without differentiation. Effective features are a suitable support structure for the cells, and an effective medium that can be added fresh to the culture without being preconditioned by another cell type. Culturing human embryonic stem cells in fresh medium according to this invention causes the cells to expand surprisingly rapidly, while retaining the ability to differentiate into cells representing all three embryonic germ layers. This new culture system allows for bulk proliferation of pPS cells for commercial production of important products for use in drug screening and human therapy.
Type:
Grant
Filed:
September 4, 2002
Date of Patent:
August 12, 2008
Assignee:
Geron Corporation
Inventors:
Ramkumar Mandalam, Chunhui Xu, Joseph D. Gold, Melissa K. Carpenter
Abstract: A synthetic, nuclear-encoded ND4 gene was linked to a mitochondrial targeting sequence and a FLAG epitope tag. This fusion construct was inserted into a rAAV vector. The ND4 fusion protein was expressed and imported into the mitochondria of cells harboring a mitochondrial DNA mutation (G11778A), where it restored cellular respiration.
Type:
Grant
Filed:
October 17, 2003
Date of Patent:
July 29, 2008
Assignee:
University of Florida Research Foundation, Inc.
Abstract: This document provides materials and methods related to PAPP-A polypeptides, aging, and transgenic non-human mammals whose genomes comprise a disrupted PAPP-A allele. Methods for making such transgenic non-human mammals, and using them and other mammals to identify and characterize agents that affect conditions related to PAPP-A activity, such as vascular restenosis, atherosclerosis, wound healing, cancer, fibrosis, bone development, fetal development, longevity, and fracture repair, also are provided.
Type:
Grant
Filed:
March 30, 2005
Date of Patent:
July 22, 2008
Assignee:
Mayo Foundation for Medical Education and Research
Abstract: The invention relates to compositions containing a polynucleotide encoding for a reporter gene, a selectable marker and a regulatory element, that provide a method for imaging cells in vivo.
Abstract: A method for producing a non-human mammalian model for neurogenic pain is provided, which includes altering a peripheral nerve of a non-human mammal by non-surgically placing a gel substance into the fascial tunnel through which the peripheral nerve passes. The placement of the gel substance leads to one or more pain behaviors thereby producing the pain model. Also provided is a non-human mammalian model for neurogenic pain so produced. Further provided is a method for screening a treatment or a therapeutic agent for efficacy in treating neurogenic pain as well as a method for screening an analgesic agent for analgesic effect in neurogenic pain.
Abstract: The present invention relates to novel immortalized precursor cell populations derived from embryonic stem cell populations and methods to produce such cell populations. Also disclosed is an assay to identify regulatory compounds capable of controlling cell growth for therapeutic and experimental use.
Type:
Grant
Filed:
August 13, 2002
Date of Patent:
May 20, 2008
Assignee:
National Jewish Medical and Research Center
Inventors:
Gordon M. Keller, Robert G. Hawley, Kyunghee Choi
Abstract: A gene activation/inactivation and site-specific integration system has been developed for mammalian cells. The invention system is based on the recombination of transfected sequences by FLP, a recombinase derived from Saccharomyces. In several cell lines, FLP has been shown to rapidly and precisely recombine copies of its specific target sequence. For example, a chromosomally integrated, silent ?-galactosidase reporter gene was activated for expression by FLP-mediated removal of intervening sequences to generate clones of marked cells. Alternatively, the reverse reaction can be used to target transfected DNA to specific chromosomal sites. These results demonstrate that FLP can be used, for example, to mosaically activate or inactivate transgenes for a variety of therapeutic purposes, as well as for analysis of vertebrate development.
Type:
Grant
Filed:
July 18, 2005
Date of Patent:
May 13, 2008
Assignee:
The Salk Institute for Biological Studies
Abstract: An object of the present invention is to provide a non-human animal model unresponsive to a mycoplasma-derived lipoprotein/lipopeptide, and a method for screening an inhibitor or a promoter for a response to a mycoplasma-derived lipoprotein with the use of the non-human animal model. A non-human animal model whose function of a gene that encodes a protein such as TLR6 that specifically recognizes a mycoplasma-derived lipoprotein is deficient on its chromosome, for example, a TLR6 knockout mouse, is generated. With the use of the non-human animal model unresponsive to a mycoplasma-derived lipoprotein or an immune cell such as a macrophage derived from the non-human animal model, a subject material and a mycoplasma-derived lipoprotein, a response to a mycoplasma-derived lipoprotein in the non-human animal model or the immune cell is measured/evaluated, and then an inhibitor or a promoter for a response to that is screened.
Abstract: Recombinant plasmids comprising (a) a ubiquitous promoter, (b) one fluorescent gene, the gene being operably liked to and inserted downstream of the ubiquitous promoter, (c) a skin-specific or muscle-specific promoter, and (d) another fluorescent gene, the gene being operably linked to and inserted downstream the skin-specific or muscle specific promoter. The ubiquitous promoter and the skin-specific or muscle promoter have the adverse directional property and the ubiquitous promoter and the skin-specific or muscle-specific promoter are located upstream of the fluorescent gene and the another fluorescent gene respectively so as to have the directional property which permits transcription of the genes. Host cells, transgenic fish harboring the plasmid of the invention and methods of producing a transgenic fish can be made with the plasmids of the invention.
Abstract: A method of expressing in vivo heart-specific fluorescence in transgenic line of zebrafish is developed, which provides a research model for studying heart-related gene functions and performing gene therapies in the future. The method comprises the following steps. Firstly, a plasmid is constructed. This plasmid construct includes the upstream regulatory region, the exon 1, the intron 1, and the exon 2 of cmlc2 gene, cDNA of GFP, wherein the cmlc2 gene and GFP cDNA form a cassette, and inverted terminal repeats from adeno-associated virus are flanked at both sides of this cassette. The plasmid construct is linearized and microinjected into one-celled zebrafish fertilized eggs. Lastly, the heart-specific fluorescent expressed zebrafish are selected and the germline-transmitting transgenic strain is generated.
Abstract: Preventives and/or remedies for liver diseases, which comprise monocyte chemoattractant protein-I (MCP-I) function inhibitors as active ingredients, respectively. Administration of the MCP-I function inhibitors brings about effects in preventing and/or remedying liver diseases.
Abstract: The disclosure provided herein teaches that fertile transgenic fish can be generated by nuclear transfer using cultured cells as embryonic fibroblasts.
Type:
Grant
Filed:
June 11, 2003
Date of Patent:
February 19, 2008
Assignee:
The Regents of the University of California
Abstract: The present invention is to provide TLR1 knockout mice specifically recognizing mycobacterial lipoproteins/lipopeptides, being useful to clarify the role of TLR1 in vivo, or a method for screening substances promoting or suppressing the response to mycobacterial lipoproteins/lipopeptides by using the same. TLR1 genes are separated from murine genomic library, the genomic part containing the intracellular and transmembrane domain of the TLR1 gene is replaced with a neomycin resistant gene, HSV-tk gene being gene encoding thymidine kinase into 3? end is introduced, ES cell clones having double resistance to G418 and Gancyclovir are screened, and ES cell clones are injected into the blastocyst of C57BL/6 mice, to generate TLR1 knockout mice through the germline.