Special Report on Cell BiologyWell CHOsen?Ever-more complicated biologics push technical boundaries
By Randall C Willis
“Increasingly, we see scientists addressing complicated and intractable diseases by developing complex protein therapeutics such as bi- and tri-specific proteins, DARPins, triabodies, novel scaffolds decorated with peptides, enzymes and growth factors,” says Igor Fisch, CEO of Selexis. “While this can be great news for patients, these complex molecules are often more challenging to manufacture, as most are non-natural proteins that need to be expressed at high enough levels to be commercially viable….
The life sciences industry is increasingly addressing lifethreatening diseases with sophisticated and complex protein therapeutics, such as novel scaffolds, fusion proteins, bi-specific proteins, and cytotoxic cytokines and interferons. These next-generation therapeutics, which are often difficult-to-express proteins, have been accompanied by a new set of challenges with regard to their manufacturing. Generating manufacturing cell lines that secrete high levels of intact recombinant therapeutic proteins requires more than effective and stable integration of the recombinant gene into the manufacturing cell’s genome…
Historically, transient and stable transfections have been performed for different purposes. Transient transfections can rapidly provide reasonable amounts of recombinant proteins (mg quantities) for early evaluation of their activity and typically transient transfections were used in the screening stages of a project when potential clinical candidates were being selected. Due to the time that it took to generate stable clonal cell lines (7–12 months), they were generated only when clinical candidates had been selected. Over the past 20 years, however, technological advances in the generation of stable and transient transfectants have improved productivity and reduced timelines, leading to some debate over whether it is better to use transiently or stably transfected cell lines during development.