摘要:
The present invention relates to a method for identification of a protein-protein interaction of protein interaction partners in a disease-related network of proteins comprising the steps of (a) identifying nucleic acid molecules by at least partial 5'sequencing and, optionally, additionally adding recombinantly cloned and sequenced nucleic acid molecules, wherein said nucleic acid molecules encode a selection of proteins suspected to contain one or several of said interaction partners and wherein said nucleic acid molecules are annotated with a positional information; (b) in frame cloning of the nucleic acid molecules of step (a) into prey and bait vectors, wherein one copy of each nucleic acid molecule is cloned into said prey vector and a second copy of each nucleic acid molecule is cloned into said bait vector; (c) transforming a first suitable host cell with the prey vector obtained in step (b) and a second suitable host cell with the bait vector obtained in step (b), wherein said first and said second host cell have a different genetic constitution and can be mated; (d) mating the first suitable host cell of step (c) with the second suitable host cell of step (c), and expressing the proteins encoded by the nucleic acid molecules obtained in step (b); (e) selecting the mated host cell obtained in step (d) on the basis of a selection advantage which is caused by the protein-protein interaction between the protein interaction partner encoded by the nucleic acid molecule of the prey vector contained in said cell and the protein interaction partner encoded by the nucleic acid molecule of the bait vector contained in said cell; and (f) identifying with the positional information obtained in step (a) the protein interaction partners of step (e) and thereby identifying the protein-protein interaction.
摘要:
The present invention relates to a method for generating a network of direct and indirect interaction partners of a disease-related (poly)peptide comprising the steps of (a) contacting a selection of (poly)peptides suspected to contain one or several of said direct or indirect interaction partners with said disease-related (poly)peptides and optionally with known direct or indirect interaction partners of said diseaserelated (poly)peptide under conditions that allow the interaction between interaction partners to occur; (b) detecting (poly)peptides that interact with said disease-related (poly)peptide or with said known direct or indirect interaction partners of said disease-related (poly) peptide; (c) contacting (poly)peptides detected in step (b) with a selection of (poly) peptides suspected to contain one or several (poly)peptides interacting with said (poly)peptides detected in step (b) under conditions that allow the interaction between interaction partners to occur; (d) detecting proteins that interact with said (poly) peptides detected in step (b); (e) contacting said disease related (poly)peptide and optionally said known direct or indirect interaction partners of said disease-related (poly)peptide, said (poly)peptides detected in steps (b) and (d) and a selection of proteins suspected to contain one or several (poly)peptides interacting with any of the afore mentioned (poly)peptides under conditions that allow the interaction between interaction partners to occur; (f) detecting (poly)peptides that interact with said disease-related (poly)peptide and optionally said known direct or indirect interaction partners of said disease-related (poly)peptide or with said (poly)peptides identified in step (b) or (d); and (g) generating a (poly)peptide(poly)peptide interaction network of said disease-related (poly)peptide and optionally said known direct or indirect interaction partners of said disease-related (poly)peptide and said (poly)peptides identified in steps (b), (d) and (f). Moreover, the present invention relates to a protein complex comprising at least two proteins and to methods for identifying compounds interfering with an interaction of said proteins. Finally, the present invention relates to a pharmaceutical composition and to the use of compounds identified by the present invention for the preparation of a pharmaceutical composition for the treatment of Huntington's disease.
摘要:
The present invention relates to a targeting system comprising, preferably as distinct components, (a) a transposon which is devoid of a polynucleotide encoding a functional transposase comprising a polynucleotide of interest; and (b) a fusion protein comprising (ba) a transposase or a fragment or derivative thereof having transposase function; and (bb) a DNA targeting domain; or (bc) a (poly)peptide binding domain that binds to a cellular or engineered (poly)peptide comprising a DNA targeting domain; or (bd) a (poly)peptide comprising the DNA targeting domain of (bb) or the (poly)peptide binding domain of (bc), wherein the transposase or a fragment or derivative thereof having transposase function of (a) is joined by a linker to the domain of (bb) or to the domain of (bc) or to the (poly)peptide of (bd); or (c) a polynucleotide encoding the fusion protein of (b).
摘要:
The present invention relates to novel, specifically neuronal expressed proteins with tryptophane hydroxylase activity, nucleic acid sequences, recombinant nucleic acid molecules containing these nucleic acid sequences or vectors containing these nucleic acid sequences or the recombinant nucleic acid molecules encoding for a neuronal tryptophane hydroxylase. The invention also relates to transgenic organisms containing these nucleic acid sequences, the recombinant nucleic acid molecules or the above cited vectors. The invention moreover refers to mono- or polyclonal antibodies directed against the isolated proteins. Furthermore, the invention relates to the use of these nucleic acid sequences and proteins for diagnosis, predisposition, therapy and monitoring of neuronal diseases. Possible fields of application among others are medicine and the pharmaceutical industry.
摘要:
The present invention is directed to a method of generating antigen specific T cells. Furthermore, the invention is directed to antigen specific T cells, isolated transgenic TCR's, pharmaceutical compositions containing same and their use in adoptive cell therapy. This invention in particular pertains to the use of cells co-expressing allogeneic MHC molecules and antigens to induce peptide-specific T cells from non-selected allogeneic T cell repertoires.
摘要:
The present invention pertains to novel high avidity antigen recognizing constructs, such as antibodies or T cell receptors, which specifically bind to the melanoma associated antigen (MAGE) A1. The constructs of the invention are particularly useful for the diagnosis, prevention or therapy of tumorous diseases which are characterized by the specific expression of the MAGE-A1 antigen. Furthermore provided are nucleic acids, vectors and host cells—such as CD4 or CD8 positive T cells—which encode, comprise or present the antigen recognizing constructs of the invention. The invention thus provides new means for immune therapy, specifically adoptive T cell therapy, for treating cancer.
摘要:
The present invention relates to a method for the production of novel T-cell receptors (TCR) which provide a reduced risk of adverse events in immune therapy, specifically in adoptive T cell transfer. The TCRs produced according to the method of the invention are specific for tumor cells and do not react with healthy tissue. Furthermore provided are nucleic acids encoding the TCR of the invention, vectors and host cells comprising the TCRs of the invention as well as their use is the treatment of tumorous diseases.
摘要:
The invention pertains to a means for downregulating or inhibiting or mislocalizing CAR in a cardiac cell for treating/curing a patient who has suffered or is predisposed to suffering a myocardial infarction (MI) or preventing myocardial infarction or complications thereof.