Cells and method of cell culture
The invention relates to a method of cell culture where the cells are modified to reduce the level of synthesis of growth and/or productivity inhibitors by the cell. The invention also relates to a method of cell culture for improving cell growth and productivity, in particular in fed-batch culture of mammalian cells at high cell density. The invention further relates to a method of producing cells with improved cell growth and/or productivity in cell culture and to cells obtained or obtainable by such methods.
1. A cell comprising two or more exogenous wild-type genes selected from the group consisting of Pah, PCBD1, Hpd, and Hgd, wherein expression of said two or more exogenous wild-type genes reduces the level of synthesis of growth and/or productivity inhibitors produced by the cell when compared to a cell that does not comprise said two or more exogenous wild-type genes.
2. The cell according to claim 1 , wherein the cell comprises a combination of constructs selected from the group consisting of:
(i) an expressible nucleic acid or vector construct comprising a PCDB1 gene,
(ii) an expressible nucleic acid or vector construct comprising a Pah gene,
(iii) an expressible nucleic acid or vector construct comprising a Pah gene and PCDB1 gene,
(iv) an expressible nucleic acid or vector construct comprising a Hpd gene, and
(v) an expressible nucleic acid or vector construct comprising a Hgd gene.
3. The cell of claim 1 , wherein the cell comprises the exogenous wild-type genes Pah and PCBD1.
4. The cell of claim 3 , wherein the cell further comprises an exogenous wild-type gene of at least one of Hpd or Hgd.
5. The cell of claim 3 , wherein the cell is a Chinese hamster ovary (CHO) cell or a human embryonic kidney cell (HEK)
6. The cell of claim 1 , wherein the cell comprises the four exogenous wild-type genes Pah, PCBD1, Hpd, and Hgd.
7. The cell of claim 1 , wherein the cell is a Chinese hamster ovary (CHO) cell.
8. The cell of claim 1 , wherein the cell is a human embryonic kidney cell (HEK).