Boehringer Ingelheim International Gmbh

Michaela Strotbek

Lore Florin

Hitto Kaufmann

Monilola Olayioye

Angelika Hausser

Lisa Pieper

Till Wenger

Hitto Kaufman

The invention relates to the field of cell culture technology. It concerns the knockdown, using RNA interference, or gene knockout, of activating transcription factor 6 beta (ATF6B), or the combination of ceramide synthase 2 (CERS2) and TBC1 domain family member 20 (TBC1D20) proteins, which play central roles in the cellular secretion pathway. This downregulation leads to improved secretion of biopharmaceutically relevant products produced in mammalian cells. The invention specifically relates to mammalian cells having enhanced secretion of a recombinant therapeutic protein compared to a control cell, a method of producing said mammalian cell, a method for the production of a recombinant secreted therapeutic protein and the use of said mammalian cell for increasing the yield of a recombinant secreted therapeutic protein.

Mammalian cells for producing a secreted protein

The invention concerns the field of cell culture technology. It concerns RNA having a specific sequence, expression vectors encoding the RNA, production host cell lines comprising the RNA, and methods of producing recombinant biopharmaceutical products using engineered host cell with altered levels of the RNAs, such as small non-coding RNAs, preferably microRNAs (miRNAs). The invention also relates to engineered host cells with altered levels in one or more of the RNAs. Those cell lines have improved secretion and/or growth characteristics in comparison to control cell lines.

Cell engineering using MICRORNAs

The invention relates to the field of cell culture technology. It concerns the knockdown, using RNA interference, or gene knockout, of activating transcription factor 6 beta (ATF6B), or the combination of ceramide synthase 2 (CERS2) and TBC1 domain family member 20 (TBC1 D20) proteins, which play central roles in the cellular secretion pathway. This downregulation leads to improved secretion of biopharmaceutically relevant products produced in mammalian cells. The invention specifically relates to mammalian cells having enhanced secretion of a recombinant therapeutic protein compared to a control cell, a method of producing said mammalian cell, a method for the production of a recombinant secreted therapeutic protein and the use of said mammalian cell for increasing the yield of a recombinant secreted therapeutic protein.

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Asperg, Germany

Michaela Strotbek