Streamlining hit discovery and optimization with a yoctoliter scale DNA reactor

Abstract

BACKGROUND: The field of DNA-encoded technology offers a cutting edge approach to creating 10(9) - 10(12)-size small molecule libraries for the rapid identification of drug-like hits. The YoctoReactor(®) (yR) is the newest DNA-encoded technology and features an innovative and fundamentally different design. OBJECTIVE: This technology evaluation presents the basic principles of the yR drug discovery technology platform and discusses its potential as an alternative to current hit discovery methods where high quality and selective drug-like hits can be delivered together with instant structure activity relationships (SAR). CONCLUSION: The yR controls and encodes billions of different synthesis combinatorially through self-assembly of DNA into three-dimensional DNA junctions. The center of these junctions forms a yoctoliter (10(-24) L) volume reactor where single-molecule, DNA- encoded reactions can take place. yR technology circumvents the high throughput screening process (HTS). Instead, drug-like families of hits are rapidly identified by molecular evolution in a single tube approach making it highly parallelizable and scalable. DNA-encoded technologies such as the yR, therefore, represent a solution to many of the bottlenecks in current early phase discovery and in handling the vast emerging opportunities in functional genomics, systems biology and proteomics.