摘要:
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.
摘要:
The present invention provides methods and means to increase the stability and/or the packaging capacity of recombinant adenoviruses, by overexpression of pIX in an adenoviral packaging cell, by retaining at least a part of the E1B 55K region in the recombinant adenoviral vector or by regulating pIX with a heterologous promoter. The invention further relates to methods and means for the production of such adenoviruses on complementing cell lines, wherein the early region 4 open reading frame 6 (E4-orf6) encoding nucleic acid is present in the adenovirus and wherein the E4-orf6 gene product is compatible with one or more products of the E1 gene products in the complementing cell, such that the adenoviral vector can be efficiently produced by the complementing cell.
摘要:
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 chondrocyte, said gene delivery vehicle is able to at least in part improve the counteraction of cartilage disease. In one embodiment said 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.
摘要:
In the absence of substantial sequence overlap between a recombinant adenoviral vector and the genome of a packaging cell, helper dependent El-containing particles (HDEP) can be formed at low frequency. The invention provides means and methods reducing or preventing the generation of HDEP. To this purpose, novel packaging cells and methods of making these are provided.
摘要:
The present invention provides novel methods and means for delivering a heterologous nucleic acid of interest to mesenchymal stem cells by providing recombinant adenoviral vectors provided with, or having a natural tropism for mesenchymal stem cells, typically in combination with a reduced tropism for other kinds of cells, in particular liver cells. The invention also provides mesenchymal stem cells provided with a heterologous nucleic acid through the use of a recombinant adenoviral vector according to the invention, and the use of such mesenchymal stem cells for the preparation of medicaments for the treatment of multiple sclerosis, rheumatoid arthritis, angiogenesis and bone related disorders, for instance in treatments that involve bone (re)generation.
摘要:
The present invention provides methods and means to increase the stability and/or the packaging capacity of recombinant adenoviruses, by overexpression of pIX in an adenoviral packaging cell, by retaining at least a part of the E1B 55K region in the recombinant adenoviral vector or by regulating pIX with a heterologous promoter. The invention further relates to methods and means for the production of such adenoviruses on complementing cell lines, wherein the early region 4 open reading frame 6 (E4-orf6) encoding nucleic acid is present in the adenovirus and wherein the E4-orf6 gene product is compatible with one or more products of the E1 gene products in the complementing cell, such that the adenoviral vector can be efficiently produced by the complementing cell.
摘要:
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 chondrocyte, said gene delivery vehicle is able to at least in part improve the counteraction of cartilage disease. In one embodiment said 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.
摘要:
The invention provides a method for identifying an adenoviral replicon capable of eliminating a target cell, comprising contacting a representative cell with said adenoviral replicon and observing any detrimental effect. Once said replicon has been identified, it can be used to specifically eliminate certain cells involved in disease, for instance tumor cells. Preferably, said replicon contacts, enters and replicates predominantly in diseased cells, causing a detrimental effect in said cells, while in non-diseased cells no or a tolerable detrimental effect is induced. Preferably, said adenoviral replicon comprises a recombinant adenovirus with a fusion between DNA from Ad5 and subgroup B adenoviral DNA. Methods for producing and purifying a replicon according to the invention is also herewith provided.
摘要:
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.