Modulation of lipid metabolism for protein production
AssigneeLonza Ltd.
InventorsJames Budge, Christopher Mark Smales, Tanya Jeane Knight, Robert Young
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Abstract
The present disclosure features methods and compositions for modulating lipid metabolism to achieve improved production and quality of recombinant products, such as next generation biologics. Modulation of lipid metabolism as described herein includes, for example, introducing a lipid metabolism modulator described herein to a cell or a cell-free system. Also encompassed by the present disclosure are engineered cells with improved production capacity and improved product quality, methods for engineering such cells, and preparations and mixtures comprising the products from such cells.
Claims44
A method for producing a recombinant polypeptide by a cell, comprising:
- i) providing a cell comprising a modification that modulates lipid metabolism, and
- ii) culturing the cell under conditions suitable for modulation of lipid metabolism by the modification,
- thereby producing the recombinant polypeptide.
A method of engineering a cell having increased production capacity and/or improved quality of production comprising introducing to the cell an exogenous nucleic acid encoding a lipid metabolism modulator, thereby engineering a cell having increased production capacity and/or improved quality of production.
A cell comprising an exogenous nucleic acid encoding a lipid metabolism modulator (LMM), wherein the exogenous nucleic acid encoding a lipid metabolism modulator is integrated into the chromosomal genome of the cell.
A CHO cell engineered to express a lipid metabolism modulator (LMM), wherein the LMM modulates one or more characteristics of the CHO cell, wherein the engineered CHO cell is selected based on modulation of one or more characteristics selected from the group consisting of:
- i) the expression of a component involved in a lipid metabolism pathway;
- ii) the activity of a component involved in a lipid metabolism pathway;
- iii) the amount of lipids present in a cell;
- iv) the amount of lipid rafts or rate of lipid raft formation;
- v) the fluidity, permeability, and/or thickness of a cell membrane;
- vi) the conversion of saturated lipids to unsaturated lipids or conversion of unsaturated lipids to saturated lipids;
- vii) the amount of saturated lipids or unsaturated lipids;
- viii) the composition of lipids in the cell to attain a favorable composition that increases ER activity;
- ix) the expansion of the ER;
- x) the expansion of the Golgi;
- xi) the amount of secretory vesicles or the formation of secretory vesicles;
- xii) the amount or rate of secretion of the product;
- xiii) the proliferation capacity;
- xiv) culture viability or cell survival;
- xv) activation of membrane receptors;
- xvi) the unfolded protein response (UPR);
- xvii) the yield or rate of production of the Next generation biologic (NGB);
- xviii) the product quality;
- and/or
- xix) cell growth/proliferation or cell specific growth rate.
Dependencies are inferred from the claim text.