In one aspect, the embodiments disclosed herein relate to the production of fully-deleted adenovirus-based gen delivery vectors packaged without the use of an adenoviral helper virus, and more particularly in their use in the transfer of genes and the expression of proteins, vaccine development, and cell engineering. In another aspect, the production of adenoviral vectors deleted of all adenoviral genes is described that carry genes of interest with detrimental or toxic activities to eukaryotic cells.

This disclosure provides replication-incompetent adenoviral vectors useful in vaccine development and gene therapy. The disclosed vectors comprise a selective deletion of E3 and are particularly useful for preparation of vaccines development and for gene therapy using toxic transgene products that result in vector instability that occurs when the entire E3 domain is deleted.

The present invention relates to the preparation of mesenchymal stem cells, which are for the proliferation of viral vectors and viruses, and enable virus production and release timing control such that tumor targeting can be improved and viruses can be mass-produced. In addition, the tumorigenesis of mesenchymal stem cells of the present invention can be fundamentally blocked, safety is secured by enabling virus production and release to be controlled at desired time points, and antitumor effects can be maximized.

This invention relates to preparations comprising adenoviral vectors with modified capsid proteins. These modified capsid proteins enable customisable decoration of the adenoviral vector to be performed, enabling diverse applications from personalised cancer vaccines to targeted gene therapy vectors, and mixtures of the same. In particular, the adenoviral vectors with modified capsid proteins may be modified in the hexon and/or pIX capsid proteins. The invention makes use of peptide pairs to provide a “primed” adenovirus which is ready for decoration.

Provided herein are chimeric adenoviral vectors. The provided chimeric adenoviral vectors can be used to induce a protective immune response and/or express a transgene in a subject in need thereof.

Compositions include modified adenoviruses. Nucleotides, cells, and methods associated with the compositions, including their use as vaccines. Viral vectors using a TET promoter system and methods of producing viruses having the same.

Recombinant cells and methods therefor are contemplated that allow for rapid and high titer production of recombinant viruses, and especially replication deficient Ad5 virus. In some preferred aspects, the host cell is modified to produce an inhibitor that reduces or eliminates the expression of a therapeutic protein encoded in the virus, while in other aspects, the virus includes a gene that directly or indirectly reduces or eliminates the expression of a therapeutic protein encoded in the virus. Most preferably, shRNA encoded by the host cell will reduce or suppress expression of a payload gene encoded in the recombinant virus.

The production of gene transfer vectors that have been designed as replication deficient constructs can be inefficient, thus limiting their broad use in medicine. The present invention provides a solution to this problem. It describes how the production efficiencies can be enhanced for gene transfer vectors that are produced by the transfer of DNA and RNA into production cells. The present invention lies m the use of cell cycle control in optimizing the production of gene transfer vectors. The subject of this patent is the modification of cell growth and physiology to enhance the efficiency of vector production. An example is given for the effect of certain media components on the cell cycle and production rate of a fully deleted helper virus independent adenoviral vector. Other applications of this technology are listed.

Recombinant cells and methods therefor are contemplated that allow for rapid and high titer production of recombinant viruses, and especially replication deficient Ad5 virus. In some preferred aspects, the host cell is modified to produce an inhibitor that reduces or eliminates the expression of a therapeutic protein encoded in the virus, while in other aspects, the virus includes a gene that directly or indirectly reduces or eliminates the expression of a therapeutic protein encoded in the virus. Most preferably, shRNA encoded by the host cell will reduce or suppress expression of a payload gene encoded in the recombinant virus.

The present invention relates to compositions and methods for monitoring viral synthesis inside a host cell. Compositions of the invention act as biosensors and can detect virus synthesized in a host cell in situ.