The present invention relates to a method for mass-producing vaccinia virus using suspended cells. Although methods for producing vaccinia virus using adherent cells in the related art have limitations that are not suitable for mass production of viruses due to the characteristics of adherent cells, the present inventors have developed a technique capable of producing viruses even in a bioreactor using a low appropriate cell number, MOI, culture FBS concentration, and a medium while using suspended cells, and it was also confirmed that the present invention has high virus productivity similar to that in the case of using adherent cells. Accordingly, the technique of producing vaccinia virus using suspended cells according to the present invention enables mass production of vaccinia virus with high productivity. Since it is possible to reduce production costs and time, manpower, and the like using suspended cells, it is expected that the technique will be effectively used in clinical and commercial production fields that require mass production of vaccinia virus.

The invention relates to vectors comprising two or more homologous nucleotide sequences and methods for generating them. The invention concerns substituting bases in the homologous nucleotide sequences with different bases that do not alter the encoded amino acid sequence. The invention allows for the reduction of intramolecular recombination between homologous nucleotide sequences, in particular in mammalian cells. The invention further relates to nucleotide sequences containing substituted bases.

Provided are compounds 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.

Disclosed herein are methods and systems for manufacturing viral vectors (e.g., lentiviral vectors) using a static light scattering device in-line with a manufacturing process.

A method of producing poxviruses at an increased growth rate and/or progeny virus titer in cells, the method including: contacting a host cell with an effective amount of nucleocytoplasmic transport inhibitor; contacting the host cell with a poxvirus of interest under conditions that permit the poxvirus of interest to adsorb to the surface of the host cell; and culturing the host cell to produce progeny poxvirus of interest.

The invention relates in various aspects to a synthetic chimeric vaccinia virus or compositions comprising such viruses, and the development and use of systems and methods for producing such synthetic chimeric vaccinia viruses. The synthetic chimeric vaccinia viruses are well suited, among others, as virus vaccines or to generate an oncolytic response and pharmaceutical formulations.

Provided herein are methods of manufacturing viruses. Also provided herein are bioreactors comprising virus-infected host cells comprising viruses. In some aspects, the present disclosure relates to production of recombinant oncolytic viruses, e.g., recombinant vaccinia viruses.

Expression vectors ideal for use in vaccinating individuals against disease based on vaccinia virus and other chordopoxviruses having high expression of recombinant genes and low expression of vector genes in target animals, and low expression of recombinant genes and high expression of vector genes in cells used for propagation.

Methods for producing viruses from adherent cells are provided. The methods include releasing virus from adherent host cells grown in a bioreactor, and purifying released virus by ultrafiltration and/or diafiltration. The methods can be used to manufacture viruses, including for clinical use, at reduced cost relative to conventional virus manufacturing methods.

Provided are compounds 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.