Molecular Engineering of Functional Nucleic Acid Nanomaterials toward In Vivo Applications

Abstract

equally exciting and perhaps more challenging field of application is toward their in vivo applications, including living animals and human bodies, in diverse areas, [2] such as sensing, drug delivery, medical imaging, and cancer therapy. However, most of these nanomaterials lack selectivity toward targets of interests. Therefore, to employ these nanomaterials for a wider range of in vivo applications, various molecular engineering approaches have been employed to obtained nanomaterials functionalized with biomolecules to enable selective targeting. [3][4][5] Among these biomolecules, functional nucleic acids, or FNAs, have shown the most promise.FNAs are DNA or RNA molecules that can interact with or bind to a specific analyte, resulting in a conformational change and/or a catalytic reaction. [6] As their names suggested, ribozymes and deoxyribozymes (called DNAzyme hereafter) can act as enzymes in the presence of cofactors to catalyze various reactions, including cleavage and ligation of RNA/DNA, and phosphorylation and peroxidation of DNA. On the other hand, riboswitches and DNA aptamers are antibody-like receptors that can bind target molecules with high affinity and selectivity. Furthermore, the binding abilities of riboswitches and aptamers can be combined with the enzymatic function of ribozymes or DNAzymes to form aptazymes so that the binding of targets can inhibit or enhance the catalytic activities. These nucleic acids, including DNAzymes, aptamers, and aptazymes, are collectively known as FNAs to emphasize their functions beyond the traditional genetic storage and transformations roles for DNA and RNA. Unlike DNA and RNA inside biological systems, FNAs are isolated via a combinatorial technique known as in vitro selection, or a process also known as systematic evolution of ligands by exponential enrichment (SELEX). The discovery of new functions of nucleic acids has not only resulted in major advances in the fields of molecular biology and biochemistry, but also revolutionized sensors designs for both in vitro and in vivo applications. [7,8] Over the past decade, numerous FNA-based nanomaterials have been developed. [9][10][11][12] Among these FNA-based nanosystems, the functions of FNAs can be categorized into two types: diagnostic function and therapeutic function. For the diagnostic function, the FNAs serve either as the biorecognition ligands for direct sensing and imaging of the Recent advances in nanotechnology and engineering have generated many nanomaterials with unique physical and chemical properties. Over the past decade, numerous nanomaterials are introduced into many research areas, such as sensors for environmental monitoring, food safety, point-ofcare diagnostics, and as transducers for solar energy transfer. Meanwhile, functional nucleic acids (FNAs), including nucleic acid enzymes, aptamers, and aptazymes, have attracted major attention from the biomedical community due to their unique target recognition and catalytic properties. Benefiting from the recent progress of molecular engine...

Engineering base-excised aptamers for highly specific recognition of adenosine

“…Since DNA oligonucleotides are chemically synthesized, they allow efficient mutation and modication studies. [29][30][31] Recently, it was reported that aer omitting a base on a DNA duplex or Gquadruplex, the scaffold allowed free adenosine or guanosine to re-t into the vacant site. This was achieved either by introducing an abasic-site in the duplex, [32][33][34] or by omitting a whole guanine-nucleotide in a G-quadruplex.…”

Size-selective molecular recognition based on a confined DNA molecular sieve using cavity-tunable framework nucleic acids

“…However, the biosensing application of framework nucleic acids based on sizeselective recognition has not been reported. Functional nucleic acids (FNAs) 4,45 , such as aptamers, DNAzymes, and molecular beacons, provide excellent molecular recognition ability, and play important roles in biological analysis [46][47][48][49][50] . Combining the advantage of these two kinds of nucleic acids, we herein develop a DNA molecular sieve for size-selective recognition through the site-specific encapsulation of functional nucleic acids in cavitytunable framework nucleic acids in an efficient and controlled manner.…”

Chemically modified nucleic acid biopolymers used in biosensing

“…Nucleic acid biopolymers show recognition ability to target molecules with good selectivity. 93 The addition of chemical modifications can impart new chemical properties and biological functions to nucleic acid biopolymers. 94,95 Therefore, the chemically modified nucleic acid biopolymers hold great potential to realize multifunctional biosensing.…”