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Rapid Antibody Glycoengineering in Chinese Hamster Ovary Cells
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Rapid Antibody Glycoengineering in Chinese Hamster Ovary Cells

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

Sowmya Balasubramanian1, Robert B Peery2, Jeremy Minshull3

  • 1Bioprocess Research and Development, Eli Lilly and Company, LTC-North, 1200 Kentucky AvenueIndianapolis, IN, 46221, USA.

Biotechnology Journal
|May 26, 2018
PubMed

Insights

The Leap-In Transposase efficiently generates high-titer Chinese Hamster Ovary (CHO) cell pools for therapeutic protein production. This method accelerates preclinical development by creating homogeneous cell populations with consistent product quality attributes.

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.
Keywords:
CHO poolsLeap-Inantibody productionrecombinant proteintransposon

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