Deep Sequencing Approaches to Antibody Discovery

Michael   F.   Naso; Jin      Lu; Tadas      Panavas

Abstract

Antibodies have become one of the dominant therapeutic platforms due to their safety, specificity, and efficacy. Owing to their massive potential diversity intrinsic to their structure, the number of possible different molecules that could be generated and analyzed from natural or synthetic systems is almost limitless. However, even with vast improvements in automation, classic antibody generation and analysis systems are severely limited in the number of molecules that can be interrogated during a typical discovery campaign. When one considers more complex target systems, along with the desire to isolate antibodies with very unique characteristics, the chances are very low that these systems will be successful. Next generation sequencing technologies (also referred to as “deep sequencing”) allow for the analysis of single molecules in millions in a very short period of time. By applying these deep sequencing technologies to antibody discovery, we now have the ability to look for very specific molecules with very unique properties and activities, further our understanding of species and strain specific repertoires, and can now begin to use sequence information to identify function. The application of these technologies is opening the door to the discovery of next generation antibody therapeutics.

Keywords: Antibody discovery, biotherapeutic, deep sequencing, diversity, phage display, rodent immunization.