Design and applications of synthetic biomolecular condensates

Designed biomolecular condensates are emerging condensed-phase assemblies, initially conceived to mimic cellular biomolecular condensates for use in biology-inspired applications such as delivery and storage of biomolecules. In recent years, rational design approaches informed by supramolecular chemistry and biomolecular nanotechnology, including the use of peptide and DNA nanotechnology for building-block minimalization and site-specific interactions, have evolved rapidly, going beyond the molecular basis of cellular condensates in terms of both composition and functionality. Thus, synthetic condensates are designed from diverse molecular building blocks, including single- or multicomponent polypeptides, peptides, RNA, DNA or biopolymers; moreover, their applications are continuously evolving to encompass new nanotechnology-relevant functions including biosensing and bioadhesion, where condensates offer advantages such as responsiveness, programmability and molecular compartmentalization. In this Review, we show the main concepts behind the molecular design of synthetic condensates, from biological mimicry to purely synthetic approaches. We discuss the mechanisms that allow control and regulation of condensate properties and the remaining challenges in analysing these properties. Finally, we discuss the applications of synthetic condensates thus far, the potential in leveraging condensates as platforms for nanotechnological applications, and the remaining hurdles towards realizing this promise. We also provide an overview of the patent landscape, highlighting trends in commercial development across areas such as delivery systems, microreactors and sensing technologies.