Htp platform for the genetic engineering of chinese hamster ovary cells
AssigneeZymergen Inc.
InventorsKate CAVES, Amar Singh
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Abstract
Presented herein is a high-throughput (HTP) genomic engineering platform for improving the production of therapeutic proteins in Chinese hamster ovary (CHO) cells. The disclosed HTP genomic engineering platform is computationally driven and integrates molecular biology, automation, and advanced machine learning protocols. The platform utilizes a unique suite of HTP genetic engineering tools to explore the genomic landscape associated with therapeutic protein production pathways, in order to unravel the biological drivers and disentangle the uncharacterized genetic architecture responsible for optimizing therapeutic protein production in CHO cells.
Claims30
A high-throughput (HTP) method for improving immunoglobulin expression, comprising:
- a. providing at least one cellular pathway target gene endogenous to a host cell and a promoter ladder comprising a plurality of promoters exhibiting different expression profiles;
- b. engineering the genome of the host cell, to create an initial promoter swap host cell library comprising a plurality of host cells, wherein the plurality of host cells comprises individual host cells comprising a different promoter from the promoter ladder operably linked to the target gene;
- and
- c. screening cells of the initial promoter swap host cell library for phenotypic characteristics of an immunoglobulin of interest and/or the host cell.
A HTP method for improving expression of a product of interest, comprising:
- a. providing at least one cellular pathway target gene endogenous to a host cell and a promoter ladder comprising a plurality of promoters exhibiting different expression profiles;
- b. engineering the genome of the host cell, to create an initial promoter swap host cell library comprising a plurality of host cells, wherein the plurality of host cells comprises individual host cells comprising a different promoter from the promoter ladder operably linked to the target gene;
- and
- c. screening cells of the initial promoter swap host cell library for phenotypic characteristics of a product of interest and/or the host cell.
Dependencies are inferred from the claim text.