Bicistornic Vectors + piggyBac = Improved Antibody Cell Line Production

To produce stable cell lines for monoclonal antibody production, manufacturers typically use the piggyBac transposon system. For larger, multi-specific antibodies that have payloads of three or four cistrons (sections of genes that express one complete, functional polypeptide), piggyBac is only the starting point.

For those larger, more complex antibodies, the challenges of multi-cistron vector architecture can lead to such upstream bottlenecks as unbalanced ratios of both heavy and light chains across cistrons, chain mispairing (which contributes to product heterogeneity), and genetic stability over time. Combined, they slow cell line development and hamper titer productivity.

Scientists at Sanofi’s Framingham, MA, site have developed a vector engineering strategy for multicistronic antibodies for coordinated transgene expression. It appears to improve promoter configuration and cassette topology, thus resolving those issues and improving titer productivity up to six-fold. It is, they suggest, “the first reported use of light-chain-selection marker-heavy chain topology for monoclonal antibody expression.”