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Updated: May 7, 2026

Laboratory Scale Production and Purification of a Therapeutic Antibody

Laboratory Scale Production and Purification of a Therapeutic Antibody

Published on: January 24, 2017

Optimizing Bispecific Antibody Expression via Multi-Omics Analysis and Vector Redesign.

Jeremy J Gam¹, Michelle M Chang¹, Dinghai Zheng¹

¹Asimov, Boston, Massachusetts, USA.

Biotechnology and Bioengineering

|May 6, 2026

Summary

This summary is machine-generated.

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Engineered bispecific antibodies (bsAbs) with improved expression titers were developed. Sequence-level diagnostics identified and resolved hidden liabilities, enhancing manufacturability of complex biologics.

Area of Science:

Biotechnology
Molecular Biology
Immunology

Background:

Bispecific antibodies (bsAbs) are advanced therapeutics engaging two targets.
Manufacturing complex bsAbs in Chinese hamster ovary (CHO) cells presents production challenges.
The IgG-scFv format is a common structure for bsAbs.

Purpose of the Study:

To investigate the causes of low expression titers for a specific IgG-scFv bispecific antibody candidate.
To identify sequence-level liabilities impacting biologics manufacturing.
To engineer a bispecific antibody with improved expression and manufacturability.

Main Methods:

Multi-omics analysis including RNA sequencing, splicing prediction, and motif screening.
Codon optimization assessment to evaluate usage patterns.

Keywords:

CHO expression biotherapeutic development bispecific antibodies codon optimization multi‐omics analysis ribosome pausing vector engineering

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Last Updated: May 7, 2026

Laboratory Scale Production and Purification of a Therapeutic Antibody

Laboratory Scale Production and Purification of a Therapeutic Antibody

Published on: January 24, 2017

Tracking Bispecific Antibody-Induced T Cell Trafficking Using Luciferase-Transduced Human T Cells

Tracking Bispecific Antibody-Induced T Cell Trafficking Using Luciferase-Transduced Human T Cells

Published on: May 12, 2023

Targeted protein and DNA sequence engineering for variant generation.

Main Results:

Identified aberrant splicing motifs, ribosome pausing sites, and suboptimal codon usage as causes for poor expression.
Generated a revised bispecific antibody variant through sequence engineering.
Achieved an 11-fold increase in stable expression titers for the engineered variant.

Conclusions:

Sequence-level bioinformatic and synthetic biology diagnostics can resolve hidden expression liabilities.
Targeted engineering strategies can significantly improve the manufacturability of complex biologics.
This work provides a generalizable framework for optimizing bispecific antibody production.