Читать книгу DNA- and RNA-Based Computing Systems - Группа авторов - Страница 44

Manipulation of matter at a nanometer scale is very challenging yet one of the central goals of the twenty‐first century. Particles at nanometer scale can exhibit unique phenomena. For example, they emit variable ultraviolet and visible light frequencies [1,2] and can exist in numerous intricate 3D forms [3]. These nanoparticles can be made from diverse spectra of materials including metal atoms (e.g. gold, silver, iron oxide nanoparticles) [4], lipids (e.g. micelles, liposome) [5], amino acids (e.g. antibodies) [6,7], and nucleic acids (nanostructures made of DNA, RNA, or hybrid oligonucleotides) [8]. While all previously mentioned materials could be used to synthesize or assemble particles in a controlled and preprogrammed way, nucleic acids have some particular advantages.

DNA and RNA are biopolymers with four distinct types of monomeric units or nucleotides (nts) (AGCT and AGCU) where A pairs with T (U in RNA) and G pairs with C. However, the order at which these nts are positioned within the sequence dictates stability and folding of the overall nucleic acid conformation. These specific variations are particularly important for structural RNA applications. The folding of RNA into a secondary structure can be predicted with high level of accuracy with user‐friendly and online available tools such as mfold [9] and NUPACK [10]. The folding algorithm is the same for RNA and DNA and utilizes empirically defined nearest‐neighbor thermodynamic parameters for each base pair step [11,12]. However, the RNA folding process often occurs through long‐range intramolecular interactions, as RNA is single‐stranded product in nature. For DNA, the folding process is dictated by intermolecular interaction. In addition, the computational prediction of DNA secondary structure is more accurate because only the G–C and A–T base pairs (Watson–Crick pairs) and the 10 unique base pair steps contribute to the stacking interaction of a double‐stranded helix. In RNA molecules, this process is more sophisticated due to the potential formation not only canonical (Watson–Crick pairs) but also non‐Watson–Crick base pairs as well as base triples and base quadrupoles as summarized by Leontis and Westhof [13–15].

The study of DNA nanoparticles has been one of significant interest since the early 1980s due to the progressive developmental foundation proposed by Nadrian Seeman [16,17]. Since the conceptual layout of DNA nanotechnology was proposed, widespread interest toward DNA nanotechnology [18–20] and RNA nanotechnology [21–24] has occurred in the scientific community. The design of nucleic acid nanoparticles into well‐defined two‐ or three‐dimensional shapes can be accomplished by using the DNA origami technique [25,26]. This approach utilizes designing multiple short DNA fragments (“staple” strands) that force folding of a long single‐strand DNA (DNA template) into a preprogrammed shape. Computational tools are used to calculate the placement of individual staple strands within a specific region of the DNA template, and due to Watson–Crick base pairing, the necessary sequences of all staple strands can be executed. Figure 5.1 demonstrates an example of the DNA dolphin‐shaped structure obtained by DNA origami [27]. Inspired by the DNA origami technique, researchers developed RNA origami. In this approach, RNA polymerase is implemented to transcribe a long RNA strand (RNA template) that can fold into a pre‐rendered shape at isothermal conditions without a need for staple strands [29]. More often, RNA nanoparticles are designed using known crystal structures of complex RNA molecules such as ribosomal RNA containing multiple, well‐defined, and often recurrent RNA structural motifs [30]. These motifs are then manually extracted from larger RNA complexes using 3D modeling software such as Swiss‐PDBViewer [31]. RNA motifs serve as modular building blocks that can be further interconnected to obtain a desired shape [22,28,32,33]. As a result, infinite numbers of nucleic acid nanoparticles with intricate shapes and dimensions can be modeled and assembled utilizing above techniques as exemplified in Figure 5.1. Researchers have used nucleic acids, both DNA and RNA, to fabricate artificial nucleic acid complexes for a variety of applications [34–40]. This has led to the development of therapeutic nucleic acid nanotechnology [41,42], various devices for structure probing in vitro and in vivo [43,44], and biomimetic systems [45], as well as development of nucleic acid “smart” devices capable of performing simple and complex molecular computations [43,46].

Figure 5.1 Nucleic acid nanostructure designing techniques. (a) DNA origami method was used to computationally design and assemble a dolphin‐shaped DNA nanostructure. (b) Example of RNA nanoparticle design approach. Variety of RNA tertiary structures (tecto‐RNAs) were combined to construct different nano‐objects of 1D or linear shape, 2D or polygonal shapes, and 3D shapes.

Source: (Panel a) From Andersen et al. [27]. Reprinted with the permission of American Chemical Society; (Panel b) From Grabow and Jaeger [28]. Reproduced with the permission of American Chemical Society.