Nucleic acid liquids

Abstract

The confluence of recent discoveries of the roles of biomolecular liquids in living systems and modern abilities to precisely synthesize and modify nucleic acids (NAs) has led to a surge of interest in liquid phases of NAs. These phases can be formed primarily from NAs, as driven by basepairing interactions, or from the electrostatic combination (coacervation) of negatively charged NAs and positively charged molecules. Generally, the use of sequence-engineered NAs provides the means to tune microsopic particle properties, and thus imbue specific, customizable behaviors into the resulting liquids. In this way, researchers have used NA liquids to tackle fundamental problems in the physics of finite valence soft materials, and to create liquids with novel structured and/or multi-functional properties. Here, we review this growing field, discussing the theoretical background of NA liquid phase separation, quantitative understanding of liquid material properties, and the broad and growing array of functional demonstrations in these materials. We close with a few comments discussing remaining open questions and challenges in the field.

Protein recruitment to dynamic DNA-RNA host condensates

“…DNA and RNA are particularly versatile polymers to build artificial condensates 10,11 . Through sequence design, nucleic acid molecules can be optimized to have a target secondary structure as well as specific affinity for distinct molecules, permitting the synthesis of complexes that phase separate predictably.…”

“…A productive approach to build DNA condensates is to use artificial motifs that include multiple strands of DNA that self-assemble into “nanostars” 12 . DNA nanostars interact via single-stranded sticky end overhangs at the tip of each arm, generating DNA dense compartments with variable viscoelastic properties that depend on the number of arms (typically 3-6), the arm length, and the sticky-end length and sequence 10 . The resulting DNA condensates can form and dissolve in response to changes in solvent and temperature 13 , to specific molecular inputs 14,15 , and to physical stimuli such as light 16,17 .…”