Abstract: The present invention relates to in vivo and in vitro methods, agents and compound screening assays for inducing anabolic stimulation of chondrocytes, including cartilage formation enhancing pharmaceutical compositions, and the use thereof in treating and/or preventing a disease involving a systemic or local decrease in mean cartilage thickness in a subject.

Abstract: Novel means and methods for their use are provided to determine the function of the product(s) of one or more sample nucleic acids. The sample nucleic acids are synthetic oligonucleotides, DNA, or cDNA and encode polypeptides, antisense nucleic acids, or GSEs. The sample nucleic acids are expressed in a host by a vehicle to alter at least one phenotype of the host. The altered phenotype(s) is/are identified as a means to assign a biological function to the product(s) encoded by the sample nucleic acid(s).

Abstract: The invention relates to the field of molecular genetics and medicine. In particular, the present invention relates to the field of functional genomics, i.e., to a method for the identification of genes that function in regulating bone homeostasis, such as the induction of osteogenesis. In particular, the present invention relates to polynucleotides and the encoded polypeptides that are identified in a high-throughput screen designed to detect modulation of bone alkaline phosphatase activity. Moreover, the present invention relates to vectors, host cells, antibodies and diagnostic methods for detecting diseases involving the discovered polynucleotides, and therapeutic methods for treating such diseases. The invention further relates to methods and means for drug compound screens designed to develop new therapeutic strategies.

Abstract: Isolated polynucleotides, and vectors including the same, are disclosed as useful for down-regulation of specific RNA in cells, including a first sequence of about 17 to about 23 nucleotides, complementary to said RNA, and linked to a second sequence capable of forming a loop when said second sequence is RNA. The polynucleotides include self-complementing single-stranded polynucleotides, including a third sequence linked by said second sequence where all nucleotides in said first and said third sequences are complementary. Functional genomic, diagnostic and therapeutic methods are disclosed that involve reducing the amount of a unique RNA sequence in cells using a vector encoding the self-complementing polynucleotide including a first sequence complementary to said RNA sequence. Methods are also disclosed for preparing the polynucleotides, vectors, libraries of vectors, and the temporary knock-down of proteins, such as lethal proteins, during virus or recombinant protein production.

Abstract: Methods, and compositions for use therein, for directly, rapidly, and unambiguously identifying, in a high throughput setting, unique nucleic acids involved in the process of lipid vacuole formation in cells and/or the cell differentiation process of adipogenesis, using an adenoviral vector library system. The method identifies unique nucleic acids capable of inducing lipid droplet formation in a cell, and determines whether the expression product of such a nucleic acid is secreted. Drug candidate compounds useful in the treatment of disease states such as obesity, type II diabetes and hyperglycemia are identified by the screening of compounds that either increase or decrease the formation of lipid droplets, or mRNA expression in host cells. Pharmaceutical compositions and methods of treatment comprising the polypeptides or polynucleotides identified by the methods of the present invention are disclosed.

Abstract: Abstract The invention relates to the field of molecular genetics and medicine. In particular the present invention relates to the field of functional genomics. The present invention provides the methods and means for the identification of nucleic acids and the polypeptides encoded by these nucleic acids that have a function related to the E2F pathway, which were isolated in a high-throughput screening assay using the E2F transcription factor activity as a read-out. The identified compounds are suitable drug-targets to treat human diseases.

Abstract: The invention relates to the targeted delivery of substances to cells. The invention provides a virus-like particle or gene delivery vehicle provided with a ligand capable of binding to a human amino acid transporter. Provided are, for example, ligands that can bind to the human transporter of cationic L-amino acids (hCAT1). Such hCAT1 binding molecules find applications in the design of vector systems for entry into human or primate cells. Preferred are retroviral envelope molecules, which—when incorporated in a virus particle—can infect hCAT1 positive cells at high frequencies. Also disclosed are methods for the design of such hCAT1 binding molecules.

Abstract: The invention relates to the field of molecular genetics and medicine. In particular the present invention relates to the field of functional genomics. The present invention provides the methods and means for the identification of nucleic acids and the polypeptides encoded by these nucleic acids that have a function related to the E2F pathway, which were isolated in a high-throughput screening assay using the E2F transcription factor activity as a read-out. The identified compounds are suitable drug-targets to treat human diseases.

Abstract: The present invention relates to the targeted delivery of substances to cells. The invention provides a method for selecting at least one mutant protein derived from a viral protein as a ligand capable of binding to a cell-surface receptor, comprising displaying at least one mutant of the protein on the surface of a microorganism expressing the protein, selecting at least one such mutant microorganism for its capacity to bind to the receptor, and incorporating the protein in a virus-like particle or gene delivery vehicle enabling targeting of the virus-like particle or gene delivery vehicle to cells carrying the receptor.

Abstract: Novel means and methods for their use are provided to determine the function of the product(s) of one or more sample nucleic acids. The sample nucleic acids are synthetic oligonucleotides, DNA, or cDNA and encode polypeptides, antisense nucleic acids, or GSEs. The sample nucleic acids are expressed in a host by a vehicle to alter at least one phenotype of the host. The altered phenotype(s) is/are identified as a means to assign a biological function to the product(s) encoded by the sample nucleic acid(s).

Abstract: The invention relates to the targeted delivery of substances to cells. The invention provides a virus-like particle or gene delivery vehicle provided with a ligand capable of binding to a human amino acid transporter. Provided are, for example, ligands that can bind to the human transporter of cationic L-amino acids (hCAT1). Such hCAT1 binding molecules find applications in the design of vector systems for entry into human or primate cells. Preferred are retroviral envelope molecules, which—when incorporated in a virus particle—can infect hCAT1 positive cells at high frequencies. Also disclosed are methods for the design of such hCAT1 binding molecules.

Abstract: Novel means and methods for their use are provided to determine the function of the product(s) of one or more sample nucleic acids. The sample nucleic acids are synthetic oligonucleotides, DNA, or cDNA and encode polypeptides, antisense nucleic acids, or GSEs. The sample nucleic acids are expressed in a host by a vehicle to alter at least one phenotype of the host. The altered phenotype(s) is/are identified as a means to assign a biological function to the product(s) encoded by the sample nucleic acid(s).