Dynamic and Reversible Decoration of DNA‐Based Scaffolds

Abstract

usually proceeds through the formation of non-covalent reversible interactions, they can also be designed to undergo a change in their structural configuration or functionality in response to multiple chemical and environmental stimuli. [15,16] Rational and programmable control of these supramolecular functional bio-scaffolds remain, however, challenging, and it is often difficult to achieve higher-order organization of multiple labeling groups in a versatile and dynamic way.Compared to other biomolecules employed for the self-assembly of structures and scaffolds, the use of synthetic DNA as a building block presents several advantages. First, the predictable and programmable nature of DNA-DNA base pairing allows the rational design of DNAbased structures with well-defined 2D and 3D geometry. [17,18] Second, the sequencespecific addressability of DNA strands together with the possibility to covalently attach different functional moieties on the backbone of a DNA oligonucleotide permits the controlled nanoscale decoration at specific locations on the DNA structure with several molecular labels. The above features have been successfully exploited in the last years to make DNA-based scaffolds decorated with a variety of different chemical and biological species such as antibodies, [19,20] signaling moieties, [21,22] aptamers, [23,24] virus capsids, [25,26] and proteins [27,28] that have found applications in bioimaging, drug delivery, and cancer therapeutics. [21,29,30] Despite the above examples clearly illustrating the versatility of synthetic DNA as building blocks to create molecular bio-scaffolds, the methods employed so far for the decoration of DNA-based assemblies often lack versatility and programmability, they are "static" and do not allow the replacement of the labels "on the fly" without prior structure disassembly. Developing novel approaches to control the decoration and labeling of DNA scaffolds with multiple functional moieties in a dynamic way will allow for achieving functional biomaterials with improved adaptability, precision, and sensing capabilities.Motivated by the above arguments, we demonstrate here a strategy to achieve dynamic and site-specific decoration of DNAbased scaffolds. To do so, we employed a model scaffold system DNA structure formed through the self-assembly of DNA tiles. More specifically, we have employed anti parallel double-crossover DNA tiles (DAE-E) formed through the hybridization of five different DNA strands. [31][32][33] These tiles display 4 singlestranded sticky ends (each of 5 nucleotides) that induce their An approach to achieving dynamic and reversible decoration of DNA-based scaffolds is demonstrated here. To do this, rationally engineered DNA tiles containing enzyme-responsive strands covalently conjugated to different molecular labels are employed. These strands are designed to be recognized and degraded by specific enzymes (i.e., Ribonuclease H, RNase H, or Uracil DNA Glycosylase, UDG) inducing their spontaneous de-hybridization from the assembled tile and rep...

A facile DNA coacervate platform for engineering wetting, engulfment, fusion and transient behavior

“…Building upon the RNA-triggered switchable coacervate systems, we asked whether autonomous and transient coacervate dissolution, as well as coacervate formation, would be possible by the addition of RNA trigger strands into RNase H-loaded systems 36 – 38 . Fig.…”

Decorated DNA‐Based Scaffolds as Lateral Flow Biosensors

“…In the second tile (reporter tile), instead, one of the strands is covalently conjugated to a fluorophore tag (Figures 1a, S1). The DNA scaffold formed through the self‐assembly of these two tiles will thus display two elements: the fluorophore and the anchor domain [53–55] . Through the simple hybridization of a modified DNA strand complementary to the anchor domain we can easily control the decoration of the DNA scaffold with different recognition elements (Figure 1b).…”

“…The DNA scaffold formed through the selfassembly of these two tiles will thus display two elements: the fluorophore and the anchor domain. [53][54][55] Through the simple hybridization of a modified DNA strand complementary to the anchor domain we can easily control the decoration of the DNA scaffold with different recognition elements (Figure 1b). This kind of functional scaffold can be used, for example, in a LF sandwich format (Figure 1c) in which both the scaffold and the test line of the LF strip are functionalized with a specific recognition element.…”

DNA Materials Assembled from One DNA Strand

“…Taking advantage of the rapid formation, high permeability and dual responsiveness, this hydrogel has been widely used in controlled release [28], tissue engineering [29] and 3D printing [30]. With the continuous development of DNA assembly, a variety of sophisticated structures and functional materials have been prepared to date [31][32][33][34][35][36][37][38][39][40][41][42][43][44], opening up a new frontier for macromolecular self-assembly. With the continuous development of DNA assembly, a variety of sophisticated structures and functional materials have been prepared to date [31][32][33][34][35][36][37][38][39][40][41][42][43][44], opening up a new frontier for macromolecular self-assembly.…”