As demand for recombinant therapeutic proteins increases, there is continued emphasis on shortening timelines for cell line selection and increasing productivity by cell line engineering. Classical approaches, including random integration and antibiotic selection, result in a large number of low productivity clones and an extended cell line development time. Identifying high productivity clones necessitates screening a large number of clones, i.e. searching for a needle in a haystack. Antibiotic selection is time consuming and does not necessarily result in the highest clone productivity possible. In this presentation, I will discuss approaches for cell line selection including high throughput screening technologies, targeted transgene integration and a novel cell line selection approach based on transcriptional selection. 

Learning Objectives:

1. Explain the limitations of traditional random integration and antibiotic-based selection methods in biotherapeutic cell line development.

2. Compare high-throughput screening, targeted transgene integration, and transcriptional selection approaches for identifying high-producing clones.

3. Evaluate how modern host and clone engineering strategies can shorten timelines and improve productivity in recombinant protein manufacturing.