Team:Potsdam Bioware


Antibody Generation System - Maturation, Selection and Production in CHO Cells

Project Description

Antibodies are of utmost importance for research and therapy but their generation is laborious and time consuming. We established a novel streamlined workflow for obtaining antibodies by incorporating all natural steps such as antibody maturation, selection and production in one genetic system implemented into a eukaryotic cell line. We stably transfect an antibody construct into CHO cells and mimic maturation by using the enzyme AID (activation-induced deaminase), which is known to induce somatic hypermutation. For selection, we are testing and deploying a versatile and continuous viral system as well as magnetic beads and cell sorting. Finally, a genetic switch enables the transition from surface expression to production of soluble antibodies. In addition, we pursue phage display with an antibody fragment to study mutation rate and evolution by AID in prokaryotes. Our system supersedes animal immunization and the smooth process will increase the ready availability of antibodies in various formats.

Antibody module: In the first step, an antibody gene is integrated into the genome of CHO cells.

Antibody module: The CHO cell expresses the antibody on the cell surface.

Mutation module: The enzyme AID mutates the antibody gene -> maturation

Selection Module: A virus infects cells with high affine antibodies. These cells survive.

The selected cells are switched to antibody secreting cells with Cre-recombinase.

primary contact: Kristian Müller