Generation of High Expressing Chinese Hamster Ovary Cell Pools Using the Leap-In Transposon System

Area of Science:

• Biotechnology
• Bioprocessing
• Molecular Biology

Background:

• Clonally derived cell lines (CDCL) from Chinese Hamster Ovary (CHO) are standard for therapeutic protein manufacturing.
• CHO cell pools offer a faster alternative for preclinical drug development.
• Ensuring CHO pools match CDCLs in protein titers and product quality is crucial.

Purpose of the Study:

• To evaluate the Leap-In Transposase system for generating high-titer, homogeneous CHO cell pools.
• To assess if Leap-In Transposase impacts product quality attributes (PQAs).

Main Methods:

• The Leap-In Transposase system was used to express four different proteins (three mAbs, one Bispecific mAb) in CHO cells.
• Resulting cell pools were analyzed for protein titers, homogeneity, and gene copy numbers.
• Comparison was made against control pools generated via random gene integration.

Main Results:

• Leap-In Transposase generated pool titers ranging from 2.0 to 5.0 g/L, exceeding control pool titers (1.5-3.3 g/L).
• The cell pools produced were homogeneously expressing.
• Higher titers were linked to increased IgG-LC and IgG-HC mRNA levels, with similar or lower gene copy numbers compared to controls.

Conclusions:

• The Leap-In Transposase is effective for rapidly generating high-titer, homogeneous CHO cell pools.
• This system accelerates therapeutic protein production without compromising product quality attributes.
• Leap-In Transposase offers a valuable tool for efficient preclinical drug development.