Abstract: Cells capable of at least, in part, complementing adenovirus an adenovirus defective in E2A function. Such cells include a nucleic acid-encoding adenovirus E2A or a functional part, derivative, temperature-sensitive mutation and/or analogue thereof, integrated into the cell's genome. Methods for producing an adenovirus particle/vector with a functional deletion of E2A are also disclosed. Such methods involve providing a cell with the functionally deleted adenovirus vector, culturing the cell, and harvesting viral particles. The functional deletion may comprise a deletion in E2A. The nucleic acid-encoding E2A in the cell's genome may lack sequence overlap with the vector, preventing formation of a replication-competent adenovirus or restoration of E2A function. The adenovirus vector may further include a functional deletion in the E1-region.

Abstract: The invention relates to the use of gene therapy in the treatment of aseptic loosening of orthopaedic prostheses and discloses methods of refixing such prostheses without open revision surgery. In particular, it provides adenoviral vectors and prodrugs for simultaneous, separate or sequential use in the destruction of interface tissue allowing subsequent recementing of loose prostheses in a minimally invasive manner.

Abstract: The invention relates to the use of gene therapy in the treatment of aseptic loosening of orthopaedic prostheses and discloses methods of refixing such prostheses without open revision surgery. In particular, it provides adenoviral vectors and prodrugs for simultaneous, separate or sequential use in the destruction of interface tissue allowing subsequent recementing of loose prostheses in a minimally invasive manner.

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: 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 described system produces replication-defective adenovirus. The system includes a primary cell containing a nucleotide derived from adenovirus and an isolated recombinant nucleic acid molecule for transfer into the primary cell. The isolated recombinant nucleotide is 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 nucleotide is to be transferred.

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: 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: 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 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: Cells capable of at least, in part, complementing adenovirus E2A function of an adenovirus defective in E2A function. Such cells include a nucleic acid encoding adenovirus E2A or a functional part, derivative and/or analogue thereof, integrated into the cell's genome. The cell may have E2A nucleic acid derived from a temperature sensitive adenovirus. Methods for producing an adenovirus particle containing an adenovirus vector with a functional deletion of E2A are also disclosed. Such methods involve providing a cell with the functionally deleted adenovirus vector, culturing the cell, and harvesting viral particle. The functional deletion can comprise a deletion of nucleic acid encoding E2A. In such a method, the nucleic acid encoding adenovirus E2A in the cell's genome has no sequence overlap with the vector leading to replication competent adenovirus and/or to the formation of an adenovirus vector comprising E2A function.

Abstract: Cells capable of at least, in part, complementing adenovirus E2A function of an adenovirus defective in E2A function. Such cells include a nucleic acid encoding adenovirus E2A or a functional part, derivative and/or analogue thereof, integrated into the genome of the cell. Preferably, the cell has E2A nucleic acid derived from a temperature sensitive adenovirus such as adenovirus ts125. Methods for producing an adenovirus particle containing an adenovirus vector with a finctional deletion of E2A are also disclosed. Such a method involves providing a cell as previously described with the functionally deleted adenovirus vector, culturing the cell, and harvesting the virus particle. The functional deletion can comprise a deletion of at least part of the nucleic acid encoding E2A.

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.