Cells having reduced BCAT1
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 a modified gene which reduces the level of synthesis of growth and/or productivity inhibitors by the cell, wherein the modified gene is Bcat1,
wherein the modification decreases Bcat1 gene expression, and wherein the cell expresses a heterologous recombinant protein.
2. The cell of claim 1 , wherein the modification of the Bcat1 gene comprises one or more of deletion, disruption, substitution, point mutation, multiple point mutation, insertion mutation, or frameshift mutation as applied to the Bcat1 gene.
3. The cell of claim 1 , wherein Bcat1 gene expression is less than or equal to 50 percent level of Bcat1 expression compared to unmodified cells.
4. The cell of claim 1 , wherein Bcat1 gene expression is less than or equal to 10 percent level of Bcat1 expression compared to unmodified cells.
5. The cell of claim 1 , wherein the cell is a CHO cell.
6. The cell of claim 1 , wherein the cell is a human embryonic kidney cell.
7. The cell of claim 1 , wherein the recombinant protein is an antibody.
8. The cell of claim 1 , wherein the cell is in a large scale bioreactor of at least 10 liters.
9. A cell comprising a knockdown of Bcat1 that decreases Bcat1 gene expression, wherein the cell is a CHO cell.
10. The cell of claim 9 , wherein the cell expresses a heterologous recombinant protein.
11. A cell comprising a knockdown of Bcat1 that decreases Bcat1 gene expression, wherein the cell is a human embryonic kidney cell.
12. The cell of claim 11 , wherein the cell expresses a heterologous recombinant protein.