Abstract: The present invention relates to a gene delivery vehicle comprising a recombinant adenovirus having a tropism for a primary human chondrocyte. By efficiently transducing a nucleic acid of interest into a primary chondrocytes, the gene delivery vehicle is able to at least in part improve the counteraction of cartilage disease. In one embodiment the recombinant adenovirus comprises a deletion in the gene encoding for fiber protein, which is replaced by a nucleic acid sequence encoding at least part of a fiber protein of a B-type adenovirus.

Abstract: Presented are ways to address the problem of replication competent adenovirus in adenoviral production for use with, for example, gene therapy. Packaging cells having no overlapping sequences with a selected vector and are suited for large scale production of recombinant adenoviruses. A system for use with the invention produces adenovirus incapable of replicating. The system includes a primary cell containing a nucleic acid based on or derived from adenovirus and an isolated recombinant nucleic acid molecule for transfer into the primary cell. The isolated recombinant nucleic acid molecule is based on or derived from an adenovirus, and further has at least one functional encapsidating signal, and at least one functional Inverted Terminal Repeat. The isolated recombinant nucleic acid molecule lacks overlapping sequences with the nucleic acid of the cell.

Abstract: The present invention relates to a gene delivery vehicle comprising a recombinant adenovirus having a tropism for a primary human chondrocyte. By efficiently transducing a nucleic acid of interest into a primary chondrocytes, the gene delivery vehicle is able, at least in part, to improve the cartilage disease. In one embodiment, the recombinant adenovirus has a deletion in the gene encoding the fiber protein, which is replaced by a nucleic acid sequence encoding at least part of a fiber protein of a B-type adenovirus.

Abstract: The invention provides a nucleic acid delivery vehicle with or having been provided with at least a tissue tropism for fibroblast-like or macrophage-like cells, preferably synoviocytes. In one aspect, the nucleic acid delivery vehicle is a virus capsid or a functional part, derivative and/or analogue thereof. Preferably, the virus capsid is an adenovirus capsid. Preferably, the adenovirus is a subgroup B adenovirus, such as adenovirus 16. Preferably, the tissue tropism is provided by at least a tissue tropism determining part of an adenovirus fiber protein or a functional derivative and/or analogue thereof. The invention further presents methods for the treatment of diseases, such as joint related diseases.

Abstract: The invention provides means and methods for transduction of a skeletal muscle cell and/or a muscle cell specific precursor thereof. Provided is the use of a gene delivery vehicle derived from an adenovirus, having a tropism for said cells, for the preparation of a medicament. In a preferred aspect of the invention, said gene delivery vehicle comprises at least a tropism determining part of an adenoviral fiber protein of subgroup B and/or F. More preferably, said gene delivery vehicle comprises at least part of a fiber protein of an adenovirus of stereotype (11, 16, 35, 40 and/or 51) or a functional part, derivative and/or analogue thereof.

Abstract: Adenoviral vectors can be used in vaccines to cause antigen-presenting cells to display desired antigens. Disclosed is a vector and associated methods that transduce antigen-presenting cells better than currently available vectors, enabling the vector to be delivered in lower doses, and thus improves the efficiency of adenoviral vaccine technology.

Abstract: Adenoviral vectors can be used in vaccines to cause antigen-presenting cells to display desired antigens. Disclosed is a vector and associated means and methods which transduce antigen-presenting cells better than currently available vectors, enabling the vector to be delivered in lower doses, and thus improving the efficiency of adenoviral vaccines technology.

Abstract: The problem of replication-competent adenovirus in virus production is solved in that we have developed packaging cells that have no overlapping sequences with a new basic vector and thus, are suited for safe large scale production of recombinant adenoviruses. One of the additional problems associated with the use of recombinant adenovirus vectors is the host-defense reaction against treatment with adenovirus. Another aspect of the invention involves screening recombinant adenovirus vector lots, especially those intended for clinical use, for the presence of adenovirus E1 sequences, as this will reveal replication-competent adenovirus, as well as revertant E1 adenoviruses. It is also an aspect of the present invention to molecularly characterize the revertants that are generated in the newer helper/vector combinations.

Abstract: The invention provides improved methods and products based on adenoviral materials which can advantageously be used in for instance gene therapy. In one aspect an adenoviral vector is provided which has no overlap with a suitable packaging cell line which is another aspect of the invention. This combination excludes the possibility of homologous recombination, thereby excluding the possibility of the formation of replication competent adenovirus. In another aspect an adenovirus based helper construct which by its size is incapable of being encapsidated. This helper virus can be transferred into any suitable host cell making it a packaging cell. Further, a number of useful mutations to adenoviral based materials and combinations of such mutations are disclosed, which all have in common the safety of the methods and the products, in particular avoiding the production of replication competent adenovirus and/or interference with the immune system. Further, a method of intracellular amplification is provided.

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: Presented are ways to address the problem of replication competent adenovirus in adenoviral production for use with, for example, gene therapy. Packaging cells having no overlapping sequences with a selected vector and are suited for large scale production of recombinant adenoviruses. A system for use with the invention produces adenovirus incapable of replicating. The system includes a primary cell containing a nucleic acid based on or derived from adenovirus and an isolated recombinant nucleic acid molecule for transfer into the primary cell. The isolated recombinant nucleic acid molecule is based on or derived from an adenovirus, and further has at least one functional encapsidating signal, and at least one functional Inverted Terminal Repeat. The isolated recombinant nucleic acid molecule lacks overlapping sequences with the nucleic acid of the cell.

Abstract: The present invention relates to providing human primary fibroblasts with a nucleic acid of interest with, among others, the purpose to improve the taking of for example. skin transplants. Particularly, methods of transducing fibroblasts with the nucleic acid of interest by means of gene delivery vehicles, in particular chimeric recombinant adenovirus (having an improved tropism for human primary fibroblasts) based gene delivery vehicles. The present invention is exemplified by an adenovirus serotype 5 genome based vector with an adenoviral fiber protein of a B-type or a D-type adenovirus, in particular adenovirus types 40 or 16, and wherein the nucleic acid of interest encodes a protein which improves angiogenesis and/or neurovascularization, in particular myogenin or MyoD.

Abstract: Presented are ways to address the problem of replication competent adenovirus in adenoviral production for use with, for example, gene therapy. Packaging cells having no overlapping sequences with a selected vector are suited for large scale production of recombinant adenoviruses. A system for use with the invention produces replication-defective adenovirus. The system includes a primary cell containing a nucleic acid based on or derived from adenovirus and an isolated recombinant nucleic acid molecule for transfer into the primary cell. The isolated recombinant nucleic acid molecule is based on or derived from an adenovirus, has at least one functional encapsidation signal and at least one functional Inverted Terminal Repeat, and lacks overlapping sequences with the nucleic acid of the cell. Otherwise, the overlapping sequences would enable homologous recombination leading to replication competent adenovirus in the primary cell into which the isolated recombinant nucleic acid molecule is to be transferred.

Abstract: Methods and compositions for the production of recombinant proteins in a human cell line. The methods and compositions are particularly useful for generating stable expression of human recombinant proteins of interest that are modified post-translationally, for example, by glycosylation. Such proteins may have advantageous properties in comparison with their counterparts produced in non-human systems such as Chinese hamster ovary cells.

Abstract: A method for treating of tumors, in particular malignant solid tumors, using adenovirus-derived material and IL-3, so that the adenovirus preferably encodes IL-3 activity, which is given systematically to a mammal, optionally in an isolated perfusion setting. Preferably, IL-3 activity is combined with other cytotoxic activity.

Abstract: Methods and vector systems for generating chimeric recombinant adenoviruses. These hybrid adenoviruses contain a genome that is derived from different adenovirus serotypes. In particular, novel hybrid adenoviruses are disclosed that have improved properties for gene therapy purposes. These properties include, but are not limited to, a decreased sensitivity towards neutralizing antibodies, a modified host range, a change in the titer to which adenovirus can be grown, the ability to escape trapping in the liver upon in vivo systemic delivery, and absence or decreased infection of antigen presenting cells of the immune system, such as macrophages or dendritic cells. These chimeric adenoviruses thus represent improved tools for gene therapy and vaccination, since they overcome the limitations observed with the currently used serotype subgroup C adenoviruses.

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: Methods and associated materials for transducing mesenchymal stem cells with a desired nucleic acid. Mesenchymal stem cells are a recently discovered kind of stem cell for which suitable transfer vehicles are still desired. Typical gene delivery vehicles such as the adenoviruses or adeno associated viruses have no particular tropism for mesenchymal stem cells. Also disclosed is gene therapy using adenoviruses provided with tropism for mesenchymal stem cells.

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 present invention provides methods and vector systems for the generation of chimeric recombinant adenoviruses. These hybrid adenoviruses contain a genome that is derived from different adenovirus serotypes. In particular, novel hybrid adenoviruses are disclosed with improved properties for gene therapy purposes. These properties include: a decreased sensitivity towards neutralizing antibodies, a modified host range, a change in the titer to which adenovirus can be grown, the ability to escape trapping in the liver upon in vivo systemic delivery, and absence or decreased infection of antigen presenting cells (APC) of the immune system, such as macrophages or dendritic cells. These chimeric adenoviruses thus represent improved tools for gene therapy and vaccination since they overcome the limitations observed with the currently used serotype subgroup C adenoviruses.