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Examples of RNA Nano-architectures

The first tectoRNAs to be generated by RNA architectonics self-assemble through loop-receptor interfaces to form dimeric nanoparticles [103, 176] or micrometer-long RNA filaments [104, 176] (Figs 10.9p-s and 10.12). The atomic structure of a self-dimerizing loop-receptor tectoRNA particle was recently solved by NMR and shown to be in remarkable agreement with the initial 3° structure model [181] (Fig. 10.12a).

Combining rational design of well-defined RNA 3° structures with small-scale combinatorial synthesis holds promise of engineering new functional modules that can accommodate the 3° structural constraints of specific supramolecular architectures [75, 78, 79]. For example, a new class of self-folding RNA molecule similar to domain P4-P6 of the natural Tetrahymena group I ribozyme was obtained by RNA architectonics [177] and subsequently used as a scaffold for combinatorial synthesis of new catalytic modules [78].

Several programmable and addressable RNA nanoparticles have been engineered to assemble in a predictable fashion through complementary selective loop-loop interactions [35, 180, 182, 183]. The DNA-packaging motor of bacterial

Fig. 10.12 TectoRNA nano-particles and filaments. (a) 0-D: Loop-receptor dimeric tectoRNA particle: the original 3° structure model [103, 176] (left) is in remarkable agreement with the recent NMR structure of the particle [181] (right). (b) 1-D: as predicted by 3° structure modeling (right), ''H shaped'' tectoRNAs can assemble into programmable, chiral and directional RNA filaments that can be visualized byTEM (adapted from Ref. [104]).

Fig. 10.12 TectoRNA nano-particles and filaments. (a) 0-D: Loop-receptor dimeric tectoRNA particle: the original 3° structure model [103, 176] (left) is in remarkable agreement with the recent NMR structure of the particle [181] (right). (b) 1-D: as predicted by 3° structure modeling (right), ''H shaped'' tectoRNAs can assemble into programmable, chiral and directional RNA filaments that can be visualized byTEM (adapted from Ref. [104]).

Helical Nanostructures
Fig. 10.13 Programmable and addressable 2-D architectures of RNA. (a) RNA tectosquares (TS) are programmable tetrameric nanoparticles. The geometry of TS assembly can be controlled by the orientation and length of their 3 ' tail connectors [35]. (b, c) 2-D architectures of tectosquares (adapted

from Ref. [35]); (b) The first programmable RNA nano-grid with 16 distinct, addressable positions [35]. This RNA structure is aperiodic with respect of its molecular constituents. (c) Various periodic patterns generated by combination of 22 tectosquares.

10.7 Self-assembly Strategies for Building Complex Nucleic Acid Nanostructures | 315

virus phi29 contains six-DNA packaging RNAs (pRNAs), which together form a hexameric ring via loop-loop interactions. For example, pRNAs were redesigned to form a variety of predictable structures namely dimers, tetramers, triangles, rods as well as micrometer size bundles of pRNA filaments [182, 183] (Fig. 10.9v-w). Recently, controllable trimeric pRNA particles harboring therapeutic molecules, siRNAs, and a receptor-binding aptamer have been shown to act as a delivery vehicle to cancer cells and induce apoptosis [184]. Collinear kissing loop interactions can generate strong 4° interacting interfaces to promote the formation of RNA particles of different sizes [180] (Fig. 10.3). This assembly principle was used in the engineering of a versatile molecular system that takes advantage of a ''right angle'' 3° structure motif to form highly programmable square shaped tetrameric nanoparticles, called tectosquares [35] (Fig. 10.9t-u).

The high modularity and hierarchical supramolecular structure of tectosquares makes it possible to construct a large number of combinatorial variants from a limited set of tectoRNAs that assemble through strong 4° interacting loop-loop interfaces [35]. Tectosquares can display an assortment of sticky tail connectors at their corner to control the geometry, directionality and addressability of the self-assembly process (Fig. 10.13). A mixture of them can assemble further into complex 1-D and 2-D architectures with periodic and aperiodic patterns and finite dimensions (Fig. 10.13). Considering that up to 88.5 millions of distinct tectos-quares can theoretically be generated from a limited set of24 tails with two different tails orientations and sizes, an almost infinite number of complex jigsaw puzzle patterns can be designed [35].

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