Abstract: The present invention relates to expression system for establishing a transgenic differentiation-control network useful for controlling cell differentiation.

Abstract: Provided herein are generalized extracellular molecule sensors (GEMSs) and polynucleotides encoding the GEMSs. Also provided herein are methods of making and using the GEMSs, such as therapeutic and diagnostic methods.

Abstract: The present invention relates to ?-cell-mimetic cells. Methods for producing ?-cell-mimetic cells as well as methods of use of ?-cell-mimetic cells as a medicament and methods of use of ?-cell-mimetic cells for the prevention, delay of progression or treatment of a metabolic disease in a subject are also provided.

Abstract: The invention relates to vectors and mammalian cells in a system useful for switching on or switching off gene expression in response to fatty acids, and a method of treating diet-induced obesity. In particular, a synthetic intracellular lipid-sensing receptor was constructed that constantly monitors blood fatty acid levels, processes diet-associated hyperlipidemia and coordinates reversible and adjustable expression of the anorectic peptide hormone pramlintide to reduce dietary intake, blood fat levels and body weight.

Abstract: The invention relates to vectors and mammalian cells in a system useful for switching on or switching off gene expression in response to pH and gaseous carbon dioxide, taking advantage of signal transduction of the human proton-activated cell-surface receptor TDAG8, OGR1 and/or GPR4 and related receptors to chimeric promoters containing cAMP-response elements. The systems according to the invention can be used to precisely monitor culture pH within the physiologic range, or also to adjust expression by gaseous C02 which shifts the C02-bicarbonate balance towards hydrogen ions. Production of biopharmaceuticals of engineered cells cultivated in a bioreactor setup can be induced by gaseous C02. Also, implanting engineered cells provide novel treatment strategies for acidosis-related disorders and type 1 diabetes.

Abstract: The invention relates to vectors and mammalian cells in a system useful for switching on or switching off gene expression in response to fatty acids, and a method of treating diet-induced obesity. In particular, a synthetic intracellular lipid-sensing receptor was constructed that constantly monitors blood fatty acid levels, processes diet-associated hyperlipidemia and coordinates reversible and adjustable expression of the anorectic peptide hormone pramlintide to reduce dietary intake, blood fat levels and body weight.

Abstract: The invention relates to a pharmaceutical composition comprising a compound preventing EthR from binding to the ethA promoter, for example a compound of formula 1 wherein R1 is optionally substituted phenyl or optionally substituted pyridyl; R2 (CH2)n wherein n is 1, 2, 3 or 4; R3 is CH3(CH2)m wherein m is 0, 1, 2 or 3; X1 is O, S, NH, N(CH3) or CH2; and X2 is O, S or NH; in particular 2-phenylethyl butyrate, and a thioamide or thiourea of formula 2 wherein R4 is optionally substituted phenyl, optionally substituted pyridyl, optionally substituted indolyl, —NR7R8; or —NH—N?CH—R9; and substituents R5 to R9 have the meanings indicated in the description, in particular ethionamide. The pharmaceutical composition is useful, e.g., in the treatment of multidrug-resistant tuberculosis.

Abstract: The invention relates to a pharmaceutical composition comprising a compound of formula (1) wherein R1 is optionally substituted phenyl, optionally substituted pyridyl or optionally substituted indolyl; R2 is (CH2)n wherein n is 0, 1, 2, 3 or 4; R3 is (CH2)mR3A wherein m is 0, 1, 2, 3 or 4, and R3A is methyl, isopropyl, tert-butyl, OCH3, OH, optionally substituted phenoxy, C?CH, C?N, optionally substituted phenyl, furanyl or thienyl; A is a ring containing X1 with the meaning O, S, NH, N(CH3) or CH2; and X2 is O, S or NH; and a compound of formula (2) wherein R4 is optionally substituted phenyl, optionally substituted pyridyl, optionally substituted indolyl, —NR7R8; or —NH—N?CH—R9; and substituents R5 to R9 have the meanings indicated in the description, in particular ethionamide. The pharmaceutical composition is useful, e.g., in the treatment of multidrug-resistant tuberculosis.

Abstract: The invention relates to vectors and mammalian cells in a system useful for switching on or switching off gene expression in response to uric acid. In a particular embodiment the invention relates to a mammalian cell useful in detecting and/or degrading a harmful excess of uric acid comprising (a) a vector comprising a genetic code for the uricase sensor-regulator HucR from Deinococcus radiodurans R1 fused to a transactivation domain or a transrepressor domain; and (b) a vector comprising the corresponding operator sequence hucO from Deinococcus radiodurans R1 specifically binding the bacterial uric acid sensor-regulator HucR, a promoter and a polynucleotide coding for an endogenous or exogenous protein, e.g. a protein interacting with uric acid.

Abstract: The invention relates to the use of a skin permeating compound such as phloretin for controlling transgene expression under control of the Pseudomonas putida DOT-T1E-derived bacterial repressor TtgR, to a vector comprising the genetic code for the repressor TtgR fused to a transactivation or a transrepressor domain, to a vector comprising a TtgR-specific operator sequence (OTtgR), a promoter and a polynucleotide coding for an endogenous or exogenous protein, and to a mammalian cell transiently or constitutively transfected with the mentioned vectors, and to mammals comprising such cells in nano- or microcontainers.

Abstract: The invention concerns the field of cell culture technology. It concerns production host cell lines with increased expression of ribosomal RNA (rRNA) achieved through reducing expression of NoCR proteins, especially of TIP-5. Those cell lines have improved secretion and growth characteristics in comparison to control cell lines. The invention further concerns a method of producing proteins using the cells generated by the described method.

Abstract: The invention relates to microcapsules consisting of a polymer degradable by a polypeptide comprising a drug or other compound of interest and a genetically engineered cell expressing said polypeptide in response to a triggering compound, and to methods of directed release of the compound of interest. The preferred polymer is optionally modified cellulose sulfate/poly-diallyl-dimethyl-ammonium chloride. Such microcapsules are non-toxic, do not elicit an immunological response and have an extended half-life time in mammals. The expression system for cellulase is, for example, based on TET and doxycycline, or E.REX and erythromycin. In another example, expression of cellulase is triggered by luteinizing hormone, which can be used for artificial insemination with microcapsules carrying sperm.

Abstract: The invention relates to microcapsules consisting of a polymer degradable by a polypeptide comprising a drug or other compound of interest and a genetically engineered cell expressing said polypeptide in response to a triggering compound, and to methods of directed release of the compound of interest. The preferred polymer is optionally modified cellulose sulfate/poly-diallyl-dimethyl-ammonium chloride. Such microcapsules are non-toxic, do not elicit an immunological response and have an extended half-life time in mammals. The expression system for cellulase is, for example, based on TET and doxycycline, or E.REX and erythromycin. In another example, expression of cellulase is triggered by luteinizing hormone, which can be used for artificial insemination with microcapsules carrying sperm.

Abstract: The invention relates to microcapsules consisting of a polymer degradable by a polypeptide comprising a drug or other compound of interest and a genetically engineered cell expressing said polypeptide in response to a triggering compound, and to methods of directed release of the compound of interest. The preferred polymer is optionally modified cellulose sulfate/poly-diallyl-dimethyl-ammonium chloride. Such microcapsules are non-toxic, do not elicit an immunological response and have an extended half-life time in mammals. The expression system for cellulase is, for example, based on TET and doxycycline, or E.REX and erythromycin. In another example, expression of cellulase is triggered by luteinizing hormone, which can be used for artificial insemination with microcapsules carrying sperm.

Abstract: The invention concerns the field of cell culture technology. It concerns production host cell lines with increased expression of ribosomal RNA (rRNA) achieved through introduction of nucleic acids encoding UBF or reducing expression of NoRC proteins, especially of TIP-5. Those cell lines have improved secretion and growth characteristics in comparison to control cell lines. The invention further concerns a method of producing proteins using the cells generated by the described method.

Abstract: The invention relates to a pharmaceutical composition comprising a compound of formula (1) wherein R1 is optionally substituted phenyl, optionally substituted pyridyl or optionally substituted indolyl; R2 is (CH2)n wherein n is 0, 1, 2, 3 or 4; R3 is (CH2)mR3A wherein m is 0, 1, 2, 3 or 4, and R3A is methyl, isopropyl, tert-butyl, OCH3, OH, optionally substituted phenoxy, C?CH, C?N, optionally substituted phenyl, furanyl or thienyl; A is a ring containing X1 with the meaning O, S, NH, N(CH3) or CH2; and X2 is O, S or NH; and a compound of formula (2) wherein R4 is optionally substituted phenyl, optionally substituted pyridyl, optionally substituted indolyl, —NR7R8; or —NH—N?CH—R9; and substituents R5 to R9 have the meanings indicated in the description, in particular ethionamide. The pharmaceutical composition is useful, e.g., in the treatment of multidrug-resistant tuberculosis.

Abstract: The invention relates to vectors and mammalian cells in a system useful for switching on or switching off gene expression in response to uric acid. In a particular embodiment the invention relates to a mammalian cell useful in detecting and/or degrading a harmful excess of uric acid comprising (a) a vector comprising a genetic code for the uricase sensor-regulator HucR from Deinococcus radiodurans R1 fused to a transactivation domain or a transrepressor domain; and (b) a vector comprising the corresponding operator sequence hucO from Deinococcus radiodurans R1 specifically binding the bacterial uric acid sensor-regulator HucR, a promoter and a polynucleotide coding for an endogenous or exogenous protein, e.g. a protein interacting with uric acid.

Abstract: The invention relates to the use of a skin permeating compound such as phloretin for controlling transgene expression under control of the Pseudomonas putida DOT-T1E-derived bacterial repressor TtgR, to a vector comprising the genetic code for the repressor TtgR fused to a transactivation or a transrepressor domain, to a vector comprising a TtgR-specific operator sequence (OTtgR), a promoter and a polynucleotide coding for an endogenous or exogenous protein, and to a mammalian cell transiently or constitutively transfected with the mentioned vectors, and to mammals comprising such cells in nano- or microcontainers.

Abstract: The invention relates to microcapsules consisting of a polymer degradable by a polypeptide comprising a drug or other compound of interest and a genetically engineered cell expressing said polypeptide in response to a triggering compound, and to methods of directed release of the compound of interest. The preferred polymer is optionally modified cellulose sulfate/poly-diallyl-dimethyl-ammonium chloride. Such microcapsules are non-toxic, do not elicit an immunological response and have an extended half-life time in mammals. The expression system for cellulase is, for example, based on TET and doxycycline, or E.REX and erythromycin. In another example, expression of cellulase is triggered by luteinizing hormone, which can be used for artificial insemination with microcapsules carrying sperm.

Abstract: The present invention relates to a hydrogel comprising a polymer, a first polypeptide and a polypeptide binding partner, wherein the polypeptide binding partner is a second polypeptide, a nucleic acid or a small molecule, and wherein the interaction between the first polypeptide and the polypeptide binding partner stabilizes the hydrogel and is modulated by the addition of a modulating compound. A drug may be physically entrapped in the hydrogel, bound to the polymer forming the hydrogel structure, or bound to the first polypeptide or the polypeptide binding partner, and then be set free on addition of the modulating compound. Such a hydrogel comprising a drug may be injected into a patient, and drug release modulated by orally administering the modulating compound.