The present invention relates to porous cross-linked agarose gel beads which have a low agarose content, a method for the preparation of the beads and their use in chromatographic applications. The beads are suitable for the separation/purification of biomolecules from a biological sample. Due to the high porosity of the beads, they are especially suitable for separation/isolation of larger particles, such as virus particles e.g. adeno virus.

The present invention provides a method for producing a virus and a harvesting solution composition. The method includes culturing cells, wherein the cells have been inoculated with viruses or have been transfected with viral packaging elements; and contacting the cultured cells with a harvesting solution composition to harvest the viruses by one-step, wherein the harvesting solution composition comprises a trypsin, a pH buffer and optionally a nuclease, and the pH of the harvesting solution composition is greater than 7.5 and no more than 10.5. The virus production method of the present invention has advantages of simple operation, easy scale-up, stable yield and so on, and the yield is unexpectedly and significantly improved compared to the prior art, and it can ensure the integrity of the viral particles without damaging the biological activity of the viruses. Therefore, it is very suitable for large-scale production of viruses.

Methods for separating AAV empty capsids from mixtures of AAV vector particles and AAV empty capsids are described. The methods use column chromatography techniques and provide for commercially viable levels of recombinant AAV virions.

Methods of purifying adenovirus that can be performed on a large scale. The methods purify adenovirus from an adenovirus-containing sample comprising or derived from a host cell population by clarifying the sample, wherein clarification comprises depth filtration followed by microfiltration; processing the clarified sample by anion exchange chromatography; and processing the anion exchange product by tangential flow filtration (TFF) to provide a TFF product.

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.

Provided are compounds of Formula (II) that enhance the efficacy of viruses by increasing spread of the virus in cells, increasing the titer of virus in cells, or increasing the antigen expression from a virus, gene or trans-gene expression from a virus, or virus protein expression in cells. Other uses, compositions and methods of using same are also provided. ##STR00001##

This invention relates to a process for producing a library of viruses, comprising first and second culturing steps. These steps aim to promote intra-species and inter-species recombination, respectively, between double-stranded DNA viruses of the same virus family.

Provided herein are methods to characterize preparations of recombinant viral particles using analytical ultracentrifugation. Recombinant viral particles include recombinant adeno-associated viral particles, recombinant adenoviral particles, recombinant lentiviral particles and recombinant herpes simplex virus particles. Variant species of recombinant viral particles including empty capsids and recombinant viral particles with variant genomes (e.g., truncated genomes, aggregates, recombinants) can be identified and quantitated. The methods can be used to characterize preparations of recombinant viral particles regardless of the sequence of the recombinant viral genome or the serotype of the recombinant viral capsid.

The present invention relates to a cell for use in producing recombinant adenoviruses (AVs), wherein DNA molecules which are capable of producing antisense RNAs against AAV cap and AAV rep mRNAs are stably integrated into the cell's genome. The invention also relates to processes for the production of such cells and processes for using such cells in the production of recombinant AVs.

Provided is a method for preparing an adenovirus vector vaccine by means of a perfusion culture process. The method comprises a step of culturing adenovirus host cells, and in particular a step of adjusting the perfusion rate by means of at least two stages according to cell density. The method increases the single cell yield of a virus after infection and the specific activity of a virus harvest liquid while achieving high-density growth of adenovirus host cells.