Next-generation antibody discovery platforms

Abstract

Antibody discovery platforms have emerged in recent years as an important source of both therapeutic molecules and research reagents. In PNAS, Larman et al. (1) provide the foundation for the next generation of antibody production using a rationally designed, fully defined scFv library and analysis pipeline, which is optimized for analysis with short-read deep-sequencing technologies. DNA sequencing has played a pivotal role in our understanding of antibody structure function and diversification by the immune system (2). It was instrumental in the identification of antibody variable and hypervariable regions and to our understanding of the manner in which the Ig repertoire is generated (3). Remarkably, although massively parallel sequencing instrumentation was not even commercially available a few years ago, we have seen a rapid transition in high-throughput sequencing (HTS) reflecting a dynamic technology transition in this field (4). This instrumentation has been transformative for genomic research and has major consequences for the future development of antibody platforms, as evidenced by its recent application by Larman et al. (1). Integrating HTS with protein or peptide display technologies allows many of the arduous and lengthy upfront screening procedures to be by-passed or complemented. The sequence information provides valuable insights into the selection process and thereby has the potential to greatly improve library design and quality of antibody repertoires (5).