456 results about "Endoplasmic reticulum" patented technology

The present invention provides synthetic 5′UTRs comprising a first polynucleotide fragment and a second polynucleotide fragment, wherein the first polynucleotide fragment comprises at least one splice site of a first eukaryotic gene, the second polynucleotide fragment comprises at least a portion of 5′ untranslated region of a second eukaryotic gene, and the first polynucleotide fragment is located 5′ of the second polynucleotide fragment. In one embodiment, the first polynucleotide fragment comprises the second intron of a sarcoplasmic / endoplasmic reticulum calcium ATPase gene and the second polynucleotide fragment comprises at least a portion of the 5′ untranslated region (5′UTR) of a eukaryotic casein gene. The synthetic 5′UTRs are useful for increasing the expression of a transgene when positioned between a promoter and a transgene within an expression vector. The present invention also provides vectors comprising synthetic 5′UTRs and methods for increasing the expression of a transgene using synthetic 5′UTRs.

The present invention mainly provides a fusion antigen specific for a target cell comprising a ligand moiety which is capable of reacting, recognizing or binding to the receptors on the target cell, a Pseudomonas exotoxin A translocation domain II, an antigenic moiety, and a carboxyl terminal moiety which permits combination of the fusion antigen to the endoplasmic reticulum (ER) membrane of the target cell. A method of immunizing an animal using the fusion antigen is also provided.

The present invention provides transgenic plants with reduced levels of saturated fatty acids in the seed oil and methods of making these plants. The transgenic plants developed through this method contain reduced levels of saturated fatty acids in seed oil due to expression of a prokaryotic delta-9 desaturase enzyme (i.e. an enzyme that introduces cis double bonds at the delta-9 position of saturated fatty acids) operably linked with an endoplasmic reticulum retention and retrieval signal sequence. One example of the invention is a plant expressing a heterologous delta-9 desaturase enzyme from cyanobacterium Anacystis nidulans, which converts lipid-bound 16:0 and 18:0 fatty acids into corresponding 16:1 and 18:1, in operative linkage with a KKSS (SEQ ID NO:5) endoplasmic reticulum retention and retrieval signal sequence.

Cytochrome b5 (Cb5) is a haem-binding protein located in the endoplasmic reticulum (ER) and the outer mitochondrial membranes of higher eukaryotes. In higher plants, animals, and fungi, the ER resident Cb5 has been shown to play a role in desaturation of acyl CoA fatty acids. Higher plants Cb5 isoforms from plants such as soybean or Arabidopsis are capable of modulating omega-3 desaturation. Co-expression of certain Cb5 isoforms with FAD3 in a host plant results in increased production of seed oil content as well as altered ratio between different fatty acids. It is also disclosed here that overexpression of Yarrowia ACL enzymes in the plastids of a host plant helps boost the synthesis of acetyl CoA, which in turn, may lead to increased synthesis of fatty acids and enhanced oil accumulation in the seeds.

An immunotoxin for use in, and a method for treating a subject having a cancer associated with malignant B-lineage cells or an autoimmune condition, are disclosed. The immunotoxin includes (a) an anti-CD19 antibody lacking an Fc fragment, (b) a modified exotoxin A protein having both Domains II and III, but lacking Domain I, and (c) a peptide linker joining the C-terminal end of the antibody to the N-terminal end of the modified exotoxin A protein. The linker is substantially resistant to extracellular cleavage. The modified exotoxin A protein may be further modified to include a C-terminal KDEL sequence (SEQ ID NO: 6) that promotes transport of the protein to the endoplasmic reticulum of cells that have taken up the immunotoxin.

The present invention provides synthetic 5′UTRs comprising a first polynucleotide fragment and a second polynucleotide fragment, wherein the first polynucleotide fragment comprises at least one splice site of a first eukaryotic gene, the second polynucleotide fragment comprises at least a portion of 5′ untranslated region of a second eukaryotic gene, and the first polynucleotide fragment is located 5′ of the second polynucleotide fragment. In one embodiment, the first polynucleotide fragment comprises the second intron of a sarcoplasmic / endoplasmic reticulum calcium ATPase gene and the second polynucleotide fragment comprises at least a portion of the 5′ untranslated region (5′UTR) of a eukaryotic casein gene. The synthetic 5′UTRs are useful for increasing the expression of a transgene when positioned between a promoter and a transgene within an expression vector. The present invention also provides vectors comprising synthetic 5′UTRs and methods for increasing the expression of a transgene using synthetic 5′UTRs.

The present invention provides methods and compositions related to the fields of chemoinformatics, chemogenomics, drug discovery and development, and drug targeting. In particular, the present invention provides subcellular localization signals (e.g., chemical address tags) that influence (e.g., direct) subcellular and organelle level localization of associated compounds (e.g., drugs and small molecule therapeutics, radioactive species, dyes and imagining agents, proapoptotic agents, antibiotics, etc) in target cells and tissues. The compositions of the present invention modulate the pharmacological profiles of associated compounds by influencing the compound's accumulation, or exclusion, from subcellular loci such as mitochondria, endoplasmic reticulum, cytoplasm, vesicles, granules, nuclei and nucleoli and other subcellular organelles and compartments. The present invention also provides methods for identifying chemical address tags, predicting their targeting characteristics, and for rational designing chemical libraries comprising chemical address tags.

The present invention provides methods for improving the production of recombinant proteins through the use of pharmacological chaperones for the recombinant proteins. As exemplified by the present invention, the binding of a pharmacological chaperone to a recombinant protein expressed by a cell can stabilize the protein and increase export of the protein out of the cell's endoplasmic reticulum, and increase secretion of the protein by the cell.

The present invention relates to a delivery system that comprises a conjugate that facilitates the delivery of a compound such as a biologically-active macromolecule, a nucleic acid or a peptide in particular, into a cell. The present invention also relates to said conjugate for delivery of a compound, such as a biologically-active macromolecule, a nucleic acid or a peptide, into a cell. The present invention further relates to a pharmaceutical composition comprising said conjugate and to its use. The present invention also relates to a method of delivering a compound to a cell or an organism, preferably a patient. The conjugates comprise: (a) at least one module that mediates cell targeting and facilitates cellular uptake, (b) at least one module that facilitates transport to the endoplasmic reticulum (ER), (c) at least one module that mediates translocation from the ER to the cytosol, and (d) at least one compound to be delivered wherein the modules (a) to (c) and the compound (d) are linked to each other in any arrangement.

The invention relates to cellular localization signals. In particular, the invention relates to endoplasmic reticulum localization signals in monomeric or multimeric form. The localization signals are utilized as research tools or are linked to therapeutics. Disclosed are methods of making and using polypeptides and modified polypeptides as signals to localize therapeutics, experimental compounds, peptides, proteins and / or other macromolecules to the endoplasmic reticulum of eukaryotic cells. The polypeptides of the invention optionally include linkage to reporters, epitopes and / or other experimental or therapeutic molecules. The invention also encompasses polynucleotides encoding the localization signals and vectors comprising these polynucleotides.

Endoplasmic reticulum stress has been found to be associated with the genetic disease tuberous sclerosis. Tuberous sclerosis is cause by defects in the two genes, TSC1 and TSC2. Agents that modulate ER stress may be used to treat tuberous sclerosis and other hamartomatous diseases. In particular, 4-phenyl butyric acid (PBA) has been shown to reduce ER stress is TSC-deficient cells. Other compounds useful in reducing ER stress are chemical chaperones such as trimethylamine N-oxide arid glycerol may also be useful in treating tuberous sclerosis. The present invention provides methods of treating a subject suffering from tuberous sclerosis using ER stress reducers such as PBA, TUDCA, UDCA, and TMAO. Methods of screening for ER stress reducers by identifying agents that reduce levels of ER stress markers in TSC-deficient cells are also provided. These agents may find use in methods and pharmaceutical compositions for treating tuberous sclerosis.

The invention provides a fluorescent probe for detecting formaldehyde in cell endoplasmic reticulums. The chemical name of the fluorescent probe is 4-hydrazino-N-(2-aminoethyl-4-methyl benzenesulfonamido)naphthalimides, and the short name is Na-FA-ER. The invention further discloses properties and functions of the probe in the fields of fluorescence detection and bioimaging. According to the fluorescent probe, the fluorescence intensity of a probe solution is gradually strengthened along with the increase of formaldehyde concentration, so that the probe has relatively good application values in sensing detection of formaldehyde in in-vivo and in-vitro environments and has certain contribution for prevention and control work of formaldehyde.

Endoplasmic reticulum stress has been found to be associated with the genetic disease tuberous sclerosis. Tuberous sclerosis is cause by defects in the two genes, TSC1 and TSC2. Agents that modulate ER stress may be used to treat tuberous sclerosis and other hamartomatous diseases. In particular, 4-phenyl butyric acid (PBA) has been shown to reduce ER stress is TSC-deficient cells. Other compounds useful in reducing ER stress are chemical chaperones such as trimethylamine N-oxide arid glycerol may also be useful in treating tuberous sclerosis. The present invention provides methods of treating a subject suffering from tuberous sclerosis using ER stress reducers such as PBA, TUDCA, UDCA, and TMAO. Methods of screening for ER stress reducers by identifying agents that reduce levels of ER stress markers in TSC-deficient cells are also provided. These agents may find use in methods and pharmaceutical compositions for treating tuberous sclerosis.

Fusion antigen used as vaccine. The invention relates to a fusion antigen specific for a target cell. The fusion antigen contains a ligand moiety, a Pseudomonas exotoxin A translocation domain II, an antigenic moiety, and a carboxyl terminal moiety. The ligand moiety is capable of reacting, recognizing or binding to receptors on the target cell. The carboxyl terminal moiety permits retention and processing of the fusion antigen in the endoplasmic reticulum (ER) membrane of the target cell. Pharmaceutical compositions and methods of inducing an immune response using the same are also disclosed.

Targeting molecules are provided for use in delivering imaging agents to epithelial tissue. The targeting molecule comprises a polypeptide that forms a closed covalent loop, contains at least three peptide domains having β-sheet character, each of the domains being separated by domains lacking β-sheet character. The targeting molecule specifically binds to a basolateral factor attached to a basolateral domain of an epithelial cell surface causing internalization of a linked imaging agent into the cells. The polypeptide or imaging agent may be linked to a peptide amino acid sequence that directs delivery of the imaging agent to a carcinoma cell, a nucleus, or an endoplasmic reticulum.

Methods for providing transgenic plants and parts hereof that, relative to the wild type state, is modified in a complex cell wall polysaccharide structure including pectins and hemicelluloses, the modification being in the overall glycosidic linkage pattern or the monosaccharide profile, comprising transforming a plant cell with a nucleotide sequence that causes an altered production of a complex cell wall polysaccharide-modifying enzyme such as endo-rhamnogalacturonan hydrolase, an endo-rhamnogalacturonan lyase, an endo-galactanase, an endo-arabinanase, an arabinofuranosidase, a galactosidase such as a beta-galactosidase, a xylosidase and an exo-galacturosidase. The modification can occur in vivo or post harvest, in which latter case the modifying enzyme is separated in the growing plant from its substrate, e.g. by targeting the enzyme to the Golgi, the endoplasmic reticulum or a vacuole, or is in a form that is inactive in the plant. After harvest the enzyme is brought into contact with its substrate or it is activated to provide the desired post harvest modification of the cell wall polysaccharide. The transgenic plant materials have improved functionalities and are useful in food and feed manufacturing and as pharmaceutically or medically active substances.

This invention provides the methodology and agents for treating any disease or clinical condition which is at least partly the result of endoplasmic reticulum-associated retention of proteins. Thus, the methods and agents of the present invention provide for the release of normally retained proteins from the endoplasmic reticulum. The present invention is particularly useful for treating any disease or clinical condition which is at least partly the result of endoplasmic reticulum-associated retention or degradation of mis-assembled or mis-folded proteins.

The invention provides a fluorescent probe for detecting hydrogen sulfide in endoplasmic reticulum. The chemical name of the fluorescent probe is 4-azido-N-(2-aminoethyl-4-methyl benzene sulfonamido)naphthalimide, or Na-ER-H2S for short, and the molecular formula is C21H17N5O4S. The invention further discloses the response of the fluorescent probe to hydrogen sulfide in cells, and the endoplasmic reticulum positioning effect is very good. Accordingly, the fluorescent probe provided by the invention can be utilized for detecting hydrogen sulfide in the cells or other biological samples through fluorescent imaging.

A nucleic acid molecule is disclosed as containing a first nucleic acid sequence comprising a nucleotide sequence that encodes γ-zein protein, or a fragment thereof capable of directing and retaining a protein towards the endoplasmic reticulum (ER) of a plant cell; a second nucleic acid sequence containing a nucleotide sequence that encodes an amino acid sequence that is specifically cleavable by enzymatic or chemical means; and a third nucleic acid sequence containing the nucleotide sequence that encodes a peptide or protein of interest. Methods of using this nucleic acid molecule for transforming host plant cells and producing the peptide or protein of interest are also disclosed.

A method for treating HIV infection is disclosed. The method comprises administering to a patient in need thereof a therapeutically effective amount of a fusion protein comprising: a) a Pseudomonas Exotoxin A (PE) peptide comprising a binding domain and a PE translocation domain, the PE peptide being devoid of cytotoxic domain III; b) optionally gag24, being fused to the PE peptide; c) a fragment of gp120 C1 domain, being fused to the PE peptide or fused to the gag24 if the gag24 is present; d) a fragment of gp 120 C5 domain, being fused to the fragment of gp120 C1 domain; e) a fragment of gp41 amino acid sequence, being fused to the fragment of gp 120 C5 domain, and f) optionally an endoplasmic reticulum retention sequence, being fused to the C-terminus of the fragment of gp41.

Fusion antigen used as vaccine. The invention relates to a fusion antigen specific for a target cell. The fusion antigen contains a ligand moiety, a Pseudomonas exotoxin A translocation domain II, an antigenic moiety, and a carboxyl terminal moiety. The ligand moiety is capable of reacting, recognizing or binding to receptors on the target cell. The carboxyl terminal moiety permits retention and processing of the fusion antigen in the endoplasmic reticulum (ER) membrane of the target cell. Pharmaceutical compositions and methods of inducing an immune response using the same are also disclosed.

The present invention relates to methods for treating endoplasmic reticulum (ER) stress-related conditions (e.g., cancer, protein folding / misfolding disease, diabetes mellitus) and for identifying compounds for treating ER stress-related conditions in a subject (e.g., a human). The invention also provides methods for diagnosing an ER stress-related condition in a subject and kits for the treatment of same.

The present invention relates to a method of identifying compounds useful in inhibiting protein kinase-like endoplasmic reticulum protein kinase (PERK). The method comprises providing a first model comprising PERK active domains, where the said active domains are selected from the group consisting of the peptide spanning from amino acid residue Asp144 to amino acid residue Ser191 of SEQ ID NO: 1 and a peptide comprising the amino acid residue at position 7 of SEQ ID NO: 1, providing one or more candidate compounds, evaluating contact between the candidate compounds and the first model to determine which of the one or more candidate compounds have an ability to bind to and / or fit in the first model, and identifying the compounds which, based on said evaluating, have the ability to bind to and / or fit in the first model as compounds potentially useful for inhibiting PERK. The present invention further relates to compounds that can be used for inhibition of PERK, for example human PERK, and methods related to treatment of PERK-mediated diseases.

The present invention provides methods that are useful for the diagnosis of neurodegenerative disease or disorder and for the screening of compounds or therapeutic agents for treating a neurodegenerative disease or disorder. The methods pertain in part to the correlation of a neurodegenerative disease or disorder with abnormal or altered endoplasmic reticulum-mitochondrial-associated membranes (ER-MAM) integrity.

The present invention provides proteins comprising binding regions for cell-type specific targeting, Shiga toxin effector regions derived from A Subunits of members of the Shiga toxin family for providing Shiga toxin effector functions (e.g. cellular internalization and cytotoxicity), and carboxy-terminal endoplasmic reticulum localization signal motifs. The presently disclosed proteins can comprise additional exogenous materials, such as, e.g., antigens, cytotoxic agents, and detection-promoting agents, and are capable of targeted delivery of these additional exogenous materials into the interiors of target cells. The proteins of the present invention have uses in methods such as, e.g., methods involving targeted killing of target cells, delivering exogenous materials into target cells, labeling subcellular compartments of target cells, and diagnosing and / or treating a variety of conditions including cancers, tumors, other growth abnormalities, immune disorders, and microbial infections.

The invention discloses novel phosphorylation sites identified in signal transduction proteins and pathways, and provides phosphorylation-site specific antibodies and heavy-isotope labeled peptides (AQUA peptides) for the selective detection and quantification of these phosphorylated sites / proteins, as well as methods of using the reagents for such purpose. Among the phosphorylation sites identified are sites occurring in the following protein types: adaptor / scaffold proteins, adhesion / extracellular matrix protein, apoptosis proteins, calcium binding proteins, cell cycle regulation proteins, chaperone proteins, chromatin, DNA binding / repair / replication proteins, cytoskeletal proteins, endoplasmic reticulum or golgi proteins, enzyme proteins, G / regulator proteins, inhibitor proteins, motor / contractile proteins, phosphatase, protease, Ser / Thr protein kinases, Protein kinase (Tyr)s, receptor / channel / cell surface proteins, RNA binding proteins, transcriptional regulators, tumor suppressor proteins, ubiquitan conjugating system proteins and proteins of unknown function.

Compounds of Formulas I-XLIII are identified as direct inhibitors of p97 ATPase or of the degradation of a p97-dependent ubiquitin-proteasome system (UPS) substrate. Methods and compositions are disclosed for inhibiting p97 ATPase and the degradation of a p97-dependent UPS substrate, and for identifying inhibitors thereof.