| Whitehead Institute for Biomedical Research Patent applications |
| Patent application number | Title | Published |
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| 20120041048 | COMPOSITIONS AND METHODS RELATING TO miR-31 - MicroRNA-31 (miR-31), targets of miR-31, the role of miR-31 in inhibiting tumor metastasis, and the role of miR-31 target genes in promoting tumor metastasis are disclosed. | 02-16-2012 |
| 20120003243 | YEAST ECTOPICALLY EXPRESSING ABNORMALLY PROCESSED PROTEINS AND USES THEREFOR - Disclosed are yeast ectopically expressing abnormally processed proteins and methods of screening to identify compounds that modulate the function of such abnormally processed proteins in yeast. Compounds identified by such screens can be used to treat or prevent diseases associated with abnormally processed proteins or protein misfolding. Such diseases include Parkinson's Disease, Parkinson's Disease with accompanying dementia, Lewy body dementia, Alzheimer's disease with Parkinsonism, and multiple system atrophy. | 01-05-2012 |
| 20110321183 | METHODS FOR LIGATION AND USES THEREOF - The present invention relates to methods for ligation. The invention provides novel reagents and methods for ligating an acyl donor compound with an acyl acceptor compound. Provided acyl donor compounds comprise a transamidase recognition sequence that allows ligation with a nucleophilic acyl acceptor in the presence of transamidase. The invention further provides kits comprising acyl donor compounds and optionally comprising other reagents for ligation. | 12-29-2011 |
| 20110288091 | SOLUBLE MTOR COMPLEXES AND MODULATORS THEREOF - The present invention relates to small molecule modulators of mTORC1 and mTORC2, syntheses thereof, and intermediates thereto. Such small molecule modulators are useful in the treatment of proliferative diseases (e.g., benign neoplasms, cancers, inflammatory diseases, autoimmune diseases, diabetic retinopathy) and metabolic diseases. Novel small molecules are provided that inhibit one or more of mTORC1, mTORC2, and PI3K-related proteins. Novel methods of providing soluble mTORC1 and mTORC2 complexes are discussed, as well as methods of using the soluble complexes in a high-throughput manner to screen for inhibitory compounds. | 11-24-2011 |
| 20110244502 | HORMONE RESPONSIVE TISSUE CULTURE SYSTEM AND USES THEREOF - The invention provides tissue culture system for primary cells (e.g. normal mammalian primary epithelial progenitors). This system includes: a) a serum-free, chemically defined cell culture media; and, b) methods for isolation and in vitro long-term propagation of primary cells (e.g. primary epithelial cells). Primary cells so isolated and cultured can be kept undifferentiated and proliferate for many weeks (>15 weeks) or population doubling (>35 PD) without senescence, or any detectable genetic alterations. Upon changing media/culture conditions, these cells can be induced to differentiate. | 10-06-2011 |
| 20110196343 | Methods for Expansion and Analysis of Cultured Hematopoietic Stem Cells - Methods and kits for propagating hematopoietic stem cells are provided. The methods comprise culturing cells in medium comprising one or more angiopoietin-like proteins, under conditions sufficient for expansion of HSCs. Angiopoietin-like proteins include angiopoietin-like protein 2, angiopoietin-like protein 3, angiopoietin-like protein 4, angiopoietin-like protein 5, angiopoietin-like protein 7, and microfibrillar-associated glycoprotein (Mfap4). Methods for identifying hematopoietic stem cells are provided and isolated hematopoietic stem cells are also provided. | 08-11-2011 |
| 20110183860 | Protein Aggregation Domains and Methods of Use Thereof - Using the Sup35 prion proteins of two distantly related yeast species, it is established that prion replication is initiated by small elements of primary sequence, which can be identified using arrays of short peptides. Subtle differences in replication elements govern the formation of distinct aggregate conformations (prion strains) and also determine their species-specific seeding activities. A Sup35 chimera that promiscuously forms prions in more than one species does so by virtue of carrying the replication element of each species. Mutations or conditions that cause the chimera to assemble into distinct prion strains favor recognition of distinct replication elements. Therefore, subtle differences in small sequences that constitute prion replication elements encode important determinants of prion propagation and transmission. The protein aggregation domains, methods for identification thereof, and polypeptides and higher order aggregates including the protein interaction domains, as well as arrays including peptides derived from an aggregation-prone polypeptide are provided. | 07-28-2011 |
| 20110143370 | Nucleic Acids Encoding a Mammalian Raptor Polypeptide and Uses Therefor - The present invention relates to isolated raptor nucleic acid molecules of mammalian origin (e.g., human) and complements, portions and variants thereof. Another aspect of the invention are isolated raptor polypeptides of mammalian origin and portions thereof, and antibodies or antigen binding fragments thereof that specifically bind a raptor polypeptide. The present invention also relates to constructs and host cells comprising the nucleic acid molecules described herein. In addition, the present invention relates to uses of the nucleic acid and polypeptide molecules provided herein. | 06-16-2011 |
| 20110124520 | Compositions and Methods for Spatial Separation and Screening of Cells - The invention provides a method for isolating particular members from a library of variant cells in individual microreactors, wherein the phenotype of the biomolecule secreted by the cell is evaluated on the basis of multiple parameters, including substrate specificity and kinetic efficiency. | 05-26-2011 |
| 20110061119 | METHOD OF PRODUCING NON-HUMAN MAMMALS - A method of producing mutant/targeted non-human mammals, such as mutant mice that does not require production of chimera and permits the introduction of multiple mutations in embryos and, thus, avoids the necessity of breeding to combine all of the desired mutations in a single animal. The method is efficient in producing ES mice. | 03-10-2011 |
| 20110053857 | YEAST CELLS EXPRESSING TAR DNA-BINDING PROTEIN 43 AND USES THEREFOR - Disclosed are yeast cells expressing TAR DNA-binding protein 43 (TDP-43) and methods of screening yeast cells to identify compounds that prevent or suppress TDP-43-induced toxicity, compounds that inhibit the formation or maintenance of cytoplasmic inclusions of TDP-43, genetic suppressors or enhancers of TDP-43-induced toxicity, and genetic suppressors or enhancers of the formation or maintenance of cytoplasmic inclusions of TDP-43. Compounds identified by such screens can be used to treat or prevent TDP-43 proteinopathies such as frontotemporal lobar degeneration or amyotrophic lateral sclerosis. | 03-03-2011 |
| 20110027235 | Targeted integration into stem cells - Disclosed herein are methods and compositions for targeted integration of sequences of interest such as lineage-specific or cell fate reporter constructs or protein encoding sequences into stem cells. | 02-03-2011 |
| 20100310525 | WNT PATHWAY STIMULATION IN REPROGRAMMING SOMATIC CELLS - The invention provides compositions and methods of use in reprogramming somatic cells. Compositions and methods of the invention are of use, e.g., for generating or modulating (e.g., enhancing) generation of induced pluripotent stem cells by reprogramming somatic cells. The reprogrammed somatic cells are useful for a number of purposes, including treating or preventing a medical condition in an individual. The invention further provides methods for identifying an agent that reprograms somatic cells to a pluripotent state and/or enhances the speed and/or efficiency of reprogramming. Certain of the compositions and methods relate to modulating the Wnt pathway. | 12-09-2010 |
| 20100291648 | Global transcription machinery engineering - The invention relates to global transcription machinery engineering to produce altered cells having improved phenotypes. | 11-18-2010 |
| 20100273776 | INHIBITION OF ALPHA-SYNUCLEIN TOXICITY - Compounds and compositions are provided for treatment or amelioration of one or more symptoms of α-synuclein toxicity, α-synuclein mediated diseases or diseases in which α-synuclein fibrils are a symptom or cause of the disease. | 10-28-2010 |
| 20100260827 | Methods of diagnosing, preventing and treating cancer metastasis - The invention relates to methods and compositions for inhibiting metastasis, such as by inhibiting FOXC2 expression or activity. The invention further relates to methods of prognosticating, diagnosing, and assisting in the diagnosis of metastasis in an individual, or of determining the metastatic potential of a tumor. The invention further relates to methods of identifying agents which inhibit metastasis. | 10-14-2010 |
| 20100121044 | SOLID PHASE TECHNIQUE FOR SELECTIVELY ISOLATING NUCLEIC ACIDS - A method of isolating target nucleic acid molecules from a solution comprising a mixture of different size nucleic acid molecules, in the presence or absence of other biomolecules, by selectively facilitating the adsorption of a particular species of nucleic acid molecule to the functional group-coated surface of magnetically responsive paramagnetic microparticles is disclosed. Separation is accomplished by manipulating the ionic strength and polyalkylene glycol concentration of the solution to selectively precipitate, and reversibly adsorb, the target species of nucleic acid molecule, characterized by a particular molecular size, to paramagnetic microparticles, the surfaces of which act as a bioaffinity adsorbent for the nucleic acids. The target nucleic acid is isolated from the starting mixture based on molecular size and through the removal of magnetic beads to which the target nucleic acid molecules have been adsorbed. The disclosed method provides a simple, robust and readily automatable means of nucleic acid isolation and purification which produces high quality nucleic acid molecules suitable for: capillary electrophoresis, nucleotide sequencing, reverse transcription cloning the transfection, transduction or microinjection of mammalian cells, gene therapy protocols, the in vitro synthesis of RNA probes, cDNA library construction and PCR amplification. | 05-13-2010 |
| 20100105036 | SIR2 Activity - This invention relates to methods of screening compounds that modulate cellular and organismal processes by modification of the activity of SIR2 and/or transcription factors, e.g., p53, particularly methods of screening for compounds that modify lifespan and/or metabolism of a cell or an organism by modulation of the activity of SIR2 and/or transcription factors, e.g., p53, and more particularly to methods of screening for compounds that modulate the activity of Sir2 and/or transcription factors, e.g., p53. In particular, the present invention relates to a method for screening a compound, by providing a test mixture comprising a transcription factor, Sir2, and a Sir2 cofactor with the compound, and evaluating an activity of a component of the test mixture in the presence of the compound. The invention further relates to therapeutic uses of said compounds. The invention further relates to a method of modifying the acetylation status of a transcription factor binding site on histone or DNA by raising local concentrations of Sir2. | 04-29-2010 |
| 20100029003 | System and methods for identifying miRNA targets and for altering miRNA and target expression - The present invention generally relates to microRNAs such as vertebrate microRNA (miRNA), for example, mammalian miRNA. Various aspects of the invention are directed to the detection, production, or expression of miRNA. In one aspect, the invention provides systems and methods for identifying targets of miRNA sequences. For instance, in one embodiment, gene sequences comprising UTRs are compared with miRNA sequences to determine the degree of interaction, for example, by determining a free energy measurement between the miRNA sequence and the UTR, and/or by determining complementarity between at least a portion of the miRNA sequence and the UTR. In another aspect, the invention is directed to the regulation of gene expression using miRNA. For example, gene expression within a cell may be altered by exposing the cell to an oligonucleotide comprising a sequence that is substantially antisense to at least a portion of an miRNA region of the gene, for example, antisense to a 6-mer or 7-mer portion of the miRNA. In still another aspect, the invention is directed to the treatment of cancer. For instance, in one set of embodiments, an isolated oligonucleotide comprising a sequence that is substantially antisense to an miRNA, or a portion of an miRNA, is administered to a subject having or being at risk of cancer. Yet other aspects of the invention are directed to compositions or kits including oligonucleotides comprising a sequence that is substantially antisense to an miRNA (or a portion of an miRNA), methods of promoting any of the above aspects, or the like. | 02-04-2010 |
| 20090304664 | MODULATORS OF ALPHA-SYNUCLEIN TOXICITY - Disclosed are genes that, when overexpressed in cells expressing alpha-synuclein, either suppress or enhance alpha-synuclein mediated cellular toxicity. Compounds that modulate expression of these genes or activity of the encoded proteins can be used to inhibit alpha-synuclein mediated toxicity and used to treat or prevent synucleinopathies such as Parkinson's disease. Also disclosed are methods of identifying inhibitors of alpha-synuclein mediated toxicity. | 12-10-2009 |
| 20090288222 | Transgenic plants overexpressing a plant vacuolar Pyrophosphatase - Transgenic plants are described which are engineered to overexpress vacuolar H | 11-19-2009 |
| 20090214465 | Quinoxaline Derivatives as Antitumor Agents - The invention relates to methods of screening for binding partners, especially binding partners essential for the biological activity of erastin (e.g. VDACs such as VDAC3). The invention also provides reagents and methods for effective killing of cancer cells with erastin and related compounds or derivatives. | 08-27-2009 |
| 20090186843 | RNA sequence-specific mediators of RNA interference - The present invention relates to a Drosophila in vitro system which was used to demonstrate that dsRNA is processed to RNA segments 21-23 nucleotides (nt) in length. Furthermore, when these 21-23 nt fragments are purified and added back to Drosophila extracts, they mediate RNA interference in the absence of long dsRNA. Thus, these 21-23 nt fragments are the sequence-specific mediators of RNA degradation. A molecular signal, which may be their specific length, must be present in these 21-23 nt fragments to recruit cellular factors involved in RNAi. This present invention encompasses these 21-23 nt fragments and their use for specifically inactivating gene function. The use of these fragments (or chemically synthesized oligonucleotides of the same or similar nature) enables the targeting of specific mRNAs for degradation in mammalian cells, where the use of long dsRNAs to elicit RNAi is usually not practical, presumably because of the deleterious effects of the interferon response. This specific targeting of a particular gene function is useful in functional genomic and therapeutic applications. | 07-23-2009 |
| 20090172838 | Compositions and methods for efficient gene silencing in plants - This invention relates to methods for knock-down of a target gene in plants, particularly efficient and specific methods for knock-down of a target gene in plants. This invention also relates to methods for silencing endogenous plant genes or plant pathogen genes. It further relates to nucleic acid constructs (DNA, RNA) which comprise a nucleic acid sequence that corresponds to a target gene or fragment thereof flanked by two complementary sites to an smRNA, e.g., a miRNA (one complementary site is on either side of the nucleic acid sequence), resulting in, for example the configuration: complementary site—nucleic acid sequence that corresponds to a target gene—complementary site. | 07-02-2009 |
| 20090099069 | MODULATORS OF ALPHA-SYNUCLEIN TOXICITY - Disclosed are compositions and methods for modulating expression of genes that function at the step of ER of Golgi trafficking. Compounds that modulate expression of these genes of activity of the encoded proteins can be used to inhibit alpha-synuclein mediated toxicity and used to threat of prevent synucleinopathies such as Parkinson's disease. Also disclosed are methods of identifying inhibitors of alpha-synuclein mediated toxicity. | 04-16-2009 |
| 20090068111 | METHODS OF IDENTIFYING LEAD COMPOUNDS THAT MODULATE TOXICITY OF NEUROTOXIC POLYPEPTIDES - Methods of screening candidate agents to identify lead compounds for the development of therapeutic agents for the treatment of a neurodegenerative disease, such as Huntington's Disease and Parkinson's Disease and methods for identifying a mutation in, or changes in expression of, a gene associated with neurodegenerative disease, such as Huntington's Disease and Parkinson's Disease, are provided. | 03-12-2009 |
| 20080299540 | Hormone responsive tissue culture system and uses thereof - The invention provides tissue culture system for primary cells (e.g. normal mammalian primary epithelial progenitors). This system includes: a) a serum-free, chemically defined cell culture media; and, b) methods for isolation and in vitro long-term propagation of primary cells (e.g. primary epithelial cells). Primary cells so isolated and cultured can be kept undifferentiated and proliferate for many weeks (>15 weeks) or population doubling (>35 PD) without senescence, or any detectable genetic alterations. Upon changing media/culture conditions, these cells can be induced to differentiate. | 12-04-2008 |
| 20080261953 | Compounds, Compositions and Methods of Inhibiting Alpha-Synuclein Toxicity - Compounds and compositions are provided for treatment or amelioration of one or more symptoms of α-synuclein toxicity, α-synuclein mediated diseases or diseases in which α-synuclein fibrils are a symptom or cause of the disease. In one embodiment, the compounds for use in the compositions and methods are heteroaryl acylguanidines, heteroarylhydrazones, dihy-dropyridones, heteroaryl and aryl styryl ketones, and heteroarylpyrazoles. | 10-23-2008 |
| 20080260724 | Drug Induced Exposure Of The Fungal Pro-Inflammatory Molecule Beta-Glucan - Methods and reagents for screening for anti-microbial agents are provided. Diagnostic tools for assessing treatment of fungal infections are provided. Antimicrobial substances including substances useful for the treatment of fungal infections are provided. In some embodiments, the substances have antigen unmasking activity. In some embodiments the substances have fungicidal activity and surface antigen unmasking activity. | 10-23-2008 |
| 20080249129 | Compositions and Methods for Treatment of Protein Misfolding Diseases - Disclosed are compounds and conditions that either suppress or enhance toxicity in yeast cells expressing alpha synuclein or huntingtin. These compounds and conditions can be used in the development of compositions that suppress toxicity, fibril formation, and/or diseases mediated at least in part by alpha synuclein or huntingtin. | 10-09-2008 |
| 20080241822 | GENOME-WIDE LOCATION AND FUNCTION OF DNA BINDING PROTEINS - The present invention relates to a method of identifying a region (one or more) of a genome of a cell to which a protein of interest binds. In the methods described herein, DNA binding protein of a cell is linked (e.g., covalently crosslinked) to genomic DNA of a cell. The genomic DNA to which the DNA binding protein is linked is removed and combined or contacted with DNA comprising a sequence complementary to genomic DNA of the cell under conditions in which hybridization between the identified genomic DNA and the sequence complementary to genomic DNA occurs. Region(s) of hybridization are region(s) of the genome of the cell to which the protein of binds. A method of identifying a set of genes where cell cycle regulator binding correlates with gene expression and of identifying genomic targets of cell cycle transcription activators in living cells is also encompassed. | 10-02-2008 |
| 20080220454 | Identification of genotype- selective anti-tumor agents - The present invention relate to methods of identifying a genotype-selective agent. In certain embodiments, the invention relates to agents that are selectively toxic to engineered human tumorigenic cells. | 09-11-2008 |
