Abstract: The present invention relates to inducible transcription control sequences for the regulation of gene expression. Specifically, it relates to an transcription control sequence comprising at least two tet operator sequence motifs allowing the binding of tetracycline-dependent transcriptional regulators, wherein each of the tetracycline-dependent transcriptional regulators binds with respect to its neighbor to an opposite face of the DNA helix, and a minimal promoter comprising a TATA box which is linked at its 5? end to a general transcription factor binding site. Further, the present invention relates to a vector, a host cell, a plant or a non-human transgenic animal comprising the transcription control sequence. Also contemplated is a method for regulating the expression of a nucleic acid sequence being operatively linked to the transcription control sequence of the present invention in a host cell, a plant or a non-human transgenic animal.

Abstract: The present invention refers to a recombinant malaria vaccine and a method for its manufacture.

Abstract: The invention relates to a merozoite surface protein 1 (“MSP-1”) preparation of Plasmodium falciparum, said MSP-1 preparation comprising a) a purified fragment p83/30 of the gp190/MSP-1 from Plasmodium without heterologous sequences, and b) a purified fragment p38/42 of the 190/MSP-1 from Plasmodium without heterologous sequences.

Abstract: The present invention relates to inducible transcription control sequences for the regulation of gene expression. Specifically, it relates to an transcription control sequence comprising at least two tet operator sequence motifs allowing the binding of tetracycline-dependent transcriptional regulators, wherein each of the said tetracycline-dependent transcriptional regulators binds with respect to its neighbour to an opposite face of the DNA helix, and a minimal promoter comprising a TATA box which is linked at its 5? end to a general transcription factor binding site. Further, the present invention relates to a vector, a host cell, a plant or a non-human transgenic animal comprising the said transcription control sequence. Also contemplated is a method for regulating the expression of a nucleic acid sequence being operatively linked to the transcription control sequence of the present invention in a host cell, a plant or a non-human transgenic animal.

Abstract: The present invention refers to a recombinant malaria vaccine and a method for its manufacture.

Abstract: The invention relates to a method for obtaining a chromosomal locus for transgenesis of a multicellular eukaryotic organism, “MEO”, to a vector for transgenesis by homologous recombination of a MEO and to the use of such an vector for trans-genesis by homologous recombination of a MEO and to the transgenic MEO thus obtainable.

Abstract: The present invention relates, at least in part, to the use of substituted tetracycline compounds for regulation of expression of nucleic acids operably linked to a tetracycline operator system. The invention pertains to compounds used in a regulatory system which utilizes components of the Tet repressor/operator/inducer system of prokaryotes to regulate gene expression in cells. Use of certain substituted tetracycline compounds, as featured in the methods of the invention, result in improved dose-response results when compared to those for e.g., tetracycline and doxycycline. Certain methods of the invention thus allow for enhanced control of the Tet repressor/operator/inducer system in regulating gene expression in cells.

Abstract: The present invention provides a panel of transcriptional activator fusion proteins which comprises both tetracycline controlled transactivator proteins and reverse tetracycline transactivator proteins. These transactivators have novel phenotypes such as altered basal transcriptional activity in the absence of doxycycline, altered induced transcriptional activity in the presence of doxycycline, or differential induction by tetracycline and analogs of tetracycline.

Abstract: The invention relates to a method for obtaining a chromosomal locus for transgenesis of a multicellular eukaryotic organism, “MEO”, to a vector for transgenesis by homologous recombination of a MEO and to the use of such an vector for trans-genesis by homologous recombination of a MEO and to the transgenic MEO thus obtainable.

Abstract: This invention relates to recombinant viruses based on MVA, which comprise at least one nucleic acid coding for a Plasmodium falciparum MSP-1 protein, a fragment or mutein of it. Furthermore, methods for the production of the recombinant viruses, virus-containing vaccines and the use of the recombinant viruses for the prophylaxis and/or therapy of malaria are provided.

Abstract: The present invention relates to a method for producing recombinants intended for use in the complete cell-surface protein gp190/MSP1 from plasmodium, especially plasmodium falciparum, as well as the complete DNA sequence of this protein and the appropriate host organisms suited for expressing said sequence, whereby the protein concerned can be entirely synthesized outside the parasite. Also, the inventive method enables sufficient production of above-mentioned protein and its supply as a vaccine. Finally disclosed is a process for stabilizing genes with high At concentration.

Abstract: A method for regulating expression of a tet operator-linked gene in a cell of a subject is disclosed. In one embodiment, the method involves introducing into the cell a nucleic acid molecule encoding a tetracycline-controllable transactivator (tTA), the tTA comprising a Tet repressor operably linked to a polypeptide which directly or indirectly activates transcription in eucaryotic cells; and modulating the concentration of a tetracycline, or analogue thereof, in the subject. Alternatively, in another embodiment, the method involves obtaining the cell from the subject, introducing into the cell a first nucleic acid molecule which operatively links a gene to at least one tet operator sequence, introducing into the cell a second nucleic acid molecule encoding a tTA, to form a modified cell, administering the modified cell to the subject, and modulating the concentration of a tetracycline, or analogue thereof, in the subject. The first and second nucleic acid molecule can be within a single molecule (e.g.

Abstract: Recombinant manufacturing process for a complete malaria antigen gp190/MSP1 The invention concerns a recombinant manufacturing process for the complete gp190/MSP1 surface protein of Plasmodium, in particular P. falciparum, as well as the complete DNA sequence of this protein and suitable host organisms for expression of the sequence, by means of which the protein in its entirety can for the first time be synthesized outside the parasite. The invention opens up for the first time the possibility of manufacturing the gp190/MSP1 surface protein in sufficient quantity; in addition there is the matter of making gp190/MSP1 available as a vaccine. Finally the invention sets out a process for the stabilization of AT-rich genes (FIG. 1).

Abstract: The present invention provides a nonhuman animal model for investigating the cause of and the therapy for organ fibrosis. Furthermore, the invention is directed to an animal model comprising a double transgenic, nonhuman animal having the ability to develop a fibrotic phenotype in a conditional and organ-specific manner. Moreover, the invention provides a method for generating the double transgene nonhuman animal.

Abstract: A method for regulating expression of a tet operator-linked gene in a cell of a subject is disclosed. In one embodiment, the method involves introducing into the cell a nucleic acid molecule encoding a tetracycline-controllable transactivator (tTA), the tTA comprising a Tet repressor operably linked to a polypeptide which directly or indirectly activates transcription in eucaryotic cells; and modulating the concentration of a tetracycline, or analogue thereof, in the subject. Alternatively, in another embodiment, the method involves obtaining the cell from the subject, introducing into the cell a first nucleic acid molecule which operatively links a gene to at least one tet operator sequence, introducing into the cell a second nucleic acid molecule encoding a tTA, to form a modified cell, administering the modified cell to the subject, and modulating the concentration of a tetracycline, or analogue thereof, in the subject. The first and second nucleic acid molecule can be within a single molecule (e.g.

Abstract: Transgenic animals carrying a transgene comprising a nucleic acid molecule encoding protein useful for regulating the expression of genes in eukaryotic cells and organisms in a highly controlled manner are disclosed. In the regulatory system of the invention, transcription of a tet operator-linked nucleotide sequence is inhibited by a transcriptional inhibitor fuision protein composed of two polypeptides, a first polypeptide which binds to tet operator sequences and a second polypeptide which directly or indirectly inhibits transcription in eukaryotic cells. In various embodiment, the first polypeptide binds to tet operator sequences either: (i) in the absence but not the presence of tetracycline (or an analogue thereof) or (ii) in the presence but not the absence of tetracycline (or an analogue thereof). In a preferred embodiment, the transgene encoding the transcriptional inhibitor fusion protein is integrated at a predetermined location within the chromosome of the transgenic animal.

Abstract: The present invention provides a panel of transcriptional activator fusion proteins which comprises both tetracycline controlled transactivator proteins and reverse tetracycline transactivator proteins. These transactivators have novel phenotypes such as altered basal transcriptional activity in the absence of doxycycline, altered induced transcriptional activity in the presence of doxycycline, or differential induction by tetracycline and analogs of tetracycline.

Abstract: Transcriptional activators which differ in their activation potential by more than 3 orders of magnitude are provided. The transactivators are fusions between a DNA binding protein (e.g., a Tet repressor) and minimal transcriptional activation domains derived from Herpes simplex virus protein 16 (VP16). Substitution mutations at amino acid position 442 within the minimal VP16 domain provide transactivators with differing transactivation ability. Moreover, chimeric activation domains comprising both wild type and mutant minimal VP16 domains provide additional variants with differing transactivation ability. Various aspects of the invention pertain to nucleic acid molecules, vectors, host cells, fusion proteins, transgenic and homologous recombinant organisms and methods of regulating gene transcription.

Abstract: Methods of regulating gene expression in subjects using tetracycline-responsive fusion proteins are disclosed. In one embodiment, the method involves introducing into a cell the subject a nucleic acid molecule encoding a fusion protein which inhibits transcription, the fusion protein comprising a first polypeptide which binds to a tet operator sequence, operatively linked to a heterologous second polypeptide which inhibits transcription in eukaryotic cells; and modulating the concentration of a tetracycline, or analogue thereof, in the subject. The first polypeptide can binds to a tet operator sequence in the absence, but not the presence, of tetracycline. Alternatively, the first polypeptide can binds to a tet operator sequence in the presence, but not the absence, of tetracycline.

Abstract: Transgenic animals carrying a transgene comprising a nucleic acid molecule encoding protein useful for regulating the expression of genes in eukaryotic cells and organisms in a highly controlled manner are disclosed. In the regulatory system of the invention, transcription of a tet operator-linked nucleotide sequence is stimulated by a transcriptional activator fusion protein composed of two polypeptides, a first polypeptide which binds to tet operator sequences in the presence of tetracycline operatively linked to a second polypeptide activates transcription in eukaryotic cells. In a preferred embodiment, the transgene encoding the transcriptional activator fusion protein is integrated at a predetermined location within the chromosome of the transgenic animal.