Sustained and continuous production of high titers of...

C - Chemistry – Metallurgy – 12 – N

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C12N 7/00 (2006.01) A61K 31/70 (2006.01) A61K 35/12 (2006.01) A61K 48/00 (2006.01) C12M 3/00 (2006.01) C12M 3/06 (2006.01) C12N 5/00 (2006.01) C12N 5/10 (2006.01) C12N 9/78 (2006.01) C12N 15/86 (2006.01) C12N 15/867 (2006.01)

Patent

CA 2098510

2098510 9210564 PCTABS00013 This invention provides improved methods for producing high titers of recombinant viral vectors by culturing producer cells in a hollow fiber bioreactor. The titer of virus in the extra fiber space (EFS) of the hollow fiber bioreactor is sufficient to transduce target cells at a multiplicity of infection sufficient to render the transduced target cells useful for genetic therapy. In a preferred embodiment, target cells are transduced with the EFS medium from a hollow fiber bioreactor in which a producer cell line, which releases packaged retroviral vectors into the EFS, has been cultured. Lymphocytes derived from an adenosine deaminase (ADA)-deficient individual that have been transduced with EFS medium that contains retroviral vectors that include RNA that encodes ADA, express ADA at a rate comparable to that of cells from an individual who does not have ADA deficiency.

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