Engineering Aptamer Switches for Multifunctional Stimulus‐Responsive Nanosystems

Abstract

specific and strong recognition of molecular targets (i.e., aptamers), catalyze biochemical reactions (i.e., ribozymes), or form sophisticated and dynamic "smart materials" or even 3D constructs (i.e., DNA origami). [2] There is particular interest in the use of nucleic acids for the construction of molecular switches, which undergo a function-altering structural change in response to an external stimulus. [3] Many such examples exist in nature, where switches enable organisms to sense physiological changes and selectively control biological functions in response. For example, riboswitches exist naturally as domains within messenger RNA (mRNA) transcripts that can bind to specific metabolites with high specificity in order to stabilize a secondary structure that prevents subsequent translation. [4] Synthetic, engineered molecular switches based on nucleic acids can achieve even greater diversity of function. Such designs make use of aptamersnucleic acid-based affinity reagents isolated via an in vitro process of systematic evolution by exponential enrichment (SELEX), in which DNA or RNA sequences with specific ligand binding are isolated from a large pool of random sequences. [5] Aptamers have proven to be robust recognition elements due to their thermal stability, ease of synthesis, and capacity to undergo ready modification with a broad array of functional groups. Importantly, traditional selection methods can be expanded upon by innovative engineering techniques to enable the incorporation of additional functions that further extend the utility of aptamers. Aptamers can adopt various 2-and 3-D structures such as duplexes, hairpins, and G-quadruplexes, and the inducible formation and disruption of these configurations can be exploited to enable complex functions besides simple biosensing. Consequently, aptamers have been incorporated into many intricate configurations, such as logic gates and dynamic nanomachines. Various research groups have also described aptamer-based switches that undergo conformational changes in response to triggers such as shifts in pH, stimulation with light, or the presence of a specific ligand. [6] Although still a relatively young area of research, these efforts could prove highly useful for materials research-conferring even greater and more selective control over devices based on functionalized nucleic acids. Aptamers are becoming increasingly integrated with various organic and inorganic molecules in order to control the assembly and operation of novel functional Although RNA and DNA are best known for their capacity to encode biological information, it has become increasingly clear over the past few decades that these biomolecules are also capable of performing other complex functions, such as molecular recognition (e.g., aptamers) and catalysis (e.g., ribozymes). Building on these foundations, researchers have begun to exploit the predictable base-pairing properties of RNA and DNA in order to utilize nucleic acids as functional materials that can undergo a molecular "switching" ...

DNAzyme- and light-induced dissipative and gated DNA networks

“…Beyond the base-sequence dictated formation of 2D 9 and 3D 10 nucleic acid structures, functional information can be encoded into the biopolymer, such as sequence-guided biocatalytic transformations, in the presence of enzymes ( e.g. , specific cleavage by endonucleases 11 or nicking enzymes, 12 ligation in the presence of ligase 13 or polymerization using polymerase 14 ), sequence-specific recognition and binding of ligands (aptamers), 15 sequence-dictated catalytic functions 16 ( e.g. , DNAzymes or ribozymes) and sequence-guided structural reconfiguration and reversible switching of DNA nanostructures.…”

A Novel pH-Sensitive Multifunctional DNA Nanomedicine: An Enhanced and Harmless GD2 Aptamer-Mediated Strategy for Guiding Neuroblastoma Antitumor Therapy

“…28,29 Aptamers can display several defined secondary motifs and further form complex three-dimensional structures to confer these molecules the ability to recognize and bind to targets with high affinity and specificity. 28 Consequently, they are also known and function as "chemical antibodies". When compared with antibodies, aptamers have unique advantages as targeting molecules due to their high affinity for binding to target molecules, limited synthetic cost, small sizes that allow them to penetrate solid tumors and even the blood-brain barrier, non-immunogenicity that facilitates long-term therapeutic efficacy and safety, and geometrical conformational flexibility and synthetic dynamics for easy synthesis and chemical modification for various therapeutic applications.- [30][31][32] Thus, so far, however, there has been no literature reported about GD2 aptamer and GD2 aptamer-mediated drug delivery system.…”

“…In addition to antibodies, aptamers, which are targeting DNA or RNA molecules synthesized via straightforward phosphoramidite chemistry, have been rapidly developed in recent years. 28 , 29 Aptamers can display several defined secondary motifs and further form complex three-dimensional structures to confer these molecules the ability to recognize and bind to targets with high affinity and specificity. 28 Consequently, they are also known and function as “chemical antibodies”.…”

Organelle‐Specific Photoactivation of DNA Nanosensors for Precise Profiling of Subcellular Enzymatic Activity

“…[5a-c] Alternatively,g enetically encoded protein-based fluorescent sensors could provide spatial information, but they are often limited by complicated genetic fusion processes. [5d,e] Recently,there is emerging development of DNA-based probes for sensing and imaging of small molecules, [6] metal ions, [7] RNA [8] and protein [9,10] in live cells because of its high programmability,e ase of synthesis,a nd biocompatibility. [11] However,a vailable DNA-based probes that allow to visualize enzymatic activity at subcellular level are severely limited.…”