Methods of assembling modified adenoviruses, libraries of adenoviral gene modules and compositions thereof are provided herein.

The present invention relates to a nucleic acid sequence comprising a binding site operably linked to a nucleotide of interest, wherein the binding site is capable of interacting with an RNA-binding protein such that translation of the nucleotide of interest is repressed in a viral vector production cell.

Methods of assembling modified adenoviruses, libraries of adenoviral gene modules and compositions thereof are provided herein.

The present invention provides an oncolytic virus formulation and preparation method thereof. The oncolytic virus formulation comprises cell vesicles derived from apoptotic tumor cells and oncolytic viruses coated in the cell vesicles as an effective component. The oncolytic virus formulation uses cell vesicles derived from tumor cells themselves to coat the oncolytic viruses, so as to evade the body's immune system attack and can be targeted to the tumor treatment site, and improve the tumor-killing effect.

The present invention relates to a nucleic acid sequence comprising a binding site operably linked to a nucleotide of interest, wherein the binding site is capable of interacting with an RNA-binding protein such that translation of the nucleotide of interest is repressed in a viral vector production cell.

Disclosed herein are methods of making vaults and packaging one or more passenger molecules in the internal cavities of the vault particles using cell-free techniques. Vaults according to the present invention and compositions comprising the vaults are free of cellular debris.

The present invention is related to a nucleic acid molecule, which is also referred to as third nucleic acid molecule, wherein the third nucleic acid molecule comprises (1) a nucleic acid molecule comprising the following elements: (a) optionally, a first part of a genome of a virus; (b) a nucleotide sequence, preferably a genomic nucleotide sequence, or a transcription unit; (c) a regulatory nucleic acid sequence which has a regulatory activity in a prokaryote; (d) exactly one site-specific recombination site; (e) a nucleotide sequence providing for a negative selection marker; (f) a bacterial nucleotide sequence unit comprising (i) bacterial nucleotide sequences for conditional replication and (ii) a nucleotide sequence providing for a positive selection marker; (g) optionally a first restriction site; or (2) a nucleic acid molecule comprising a nucleotide sequence according to SEQ ID NO: 6; or (3) a nucleic acid molecule identical or similar to the nucleic acid molecule contained in the organism deposited with the DSMZ under the Budapest treaty under accession number DSM 23754, wherein preferably the nucleic acid molecule contained in the organism is a heterologous nucleic acid molecule; wherein the third nucleic acid molecule is either a linear or a circular molecule.

Methods for the production of adenoviruses which are suitable for use in a vaccine, and methods for increasing the yield of adenoviruses during production. These methods include adding an adenovirus to a cell population in culture; culturing the cell population under conditions which are permissive for infection of the cell population with the adenovirus to provide a cell population comprising adenovirus-infected cells; culturing the cell population comprising adenovirus-infected cells under conditions which are permissive for replication of the adenovirus; and harvesting the adenovirus from the culture.

The invention relates to a method for preparing an adenovirus comprising a) providing a host cell in a medium capable of supporting growth of said host cell b) contacting said host cell with an adenovirus c) incubating to allow infection of said cell by said adenovirus d) incubating to allow production of adenovirus by said host cell wherein said host cell is, or is derived from, a HEK293 cell, and wherein the medium comprises BalanCD HEK293. The invention also relates to adenovirus produced, and to compositions comprising said adenovirus.

The invention relates to a method for purifying an adenovirus comprising (a) providing a liquid sample comprising adenovirus, (b) clarifying said sample by depth filtration, (c) performing anion exchange chromatography comprising the steps of (i) directly applying the clarified sample of (b) to an anion exchange column, (ii) eluting adenovirus from the anion exchange column to provide an eluate. The invention also relates to adenovirus produced from said methods, and to compositions comprising same.