Functional Nucleic Acids for DNA Nanotechnology - DNA Nanotechnology: From Structure to Function - page 6

materials [ 5 , 6 ], double-crossover molecules were constructed by means of joining
two double helices together by an exchange of strands [ 7 , 8 ]. Due to the development
of different secondary rigid structures (e.g., double crossover, triple crossover)
[ 9 - 13 ], tremendous numbers of DNA nanostructures have been assembled by the
appropriate sticky ends [ 14 , 15 ]. Another significant breakthrough is the invention
of DNA origami by P. Rothemund in 2006 [ 16 ], where a long scaffold of single-
stranded DNA (ssDNA) is folded with the help of hundreds of short staple strands
into the desired 2D or 3D shapes. Since then, it has dramatically accelerated the
progress in DNA nanotechnology and greatly expanded human imagination in
nanoscale by providing such simple, precise, and faithful design principles for
generating spatially addressable nanostructures. Numerous DNA origami-based
nanostructures have been constructed, including geometrical shapes such as rect-
angle, star, and smiley face [ 16 ]; nongeometrical shapes such as maps and dolphin
[ 17 , 18 ]; as well as 3D structures such as honeycomb lattice [ 19 ], nanotube [ 20 ], box
[ 21 ], and even nanoflask [ 22 ]. Based on these DNA nanostructures, various DNA
nanodevices have been generated and used in emerging fields such as nanosensing,
nanomedicine, nanoelectronics, and nanomachines [ 23 - 26 ].
On the other side, nucleic acids have been found to possess other functions
beyond conventional genetic roles induced by Watson-Crick base pairing in the past
two decades. They can recognize a diverse range of analytes beyond complementary
DNA or RNA [ 27 ]. They can act as enzyme to catalyze various reactions, including
RNA/DNA cleavage, RNA/DNA ligation, DNA phosphorylation, and peroxidases
[ 28 ]. These nucleic acids, including aptamers, DNAzymes, and aptazymes, are
collectively called functional nucleic acids (FNAs). Since these FNAs are essentially
single-stranded oligonucleotides, compared with other functional molecules such
as small molecules, peptides, and proteins, they are ready to be engineered into
DNA nanostructures, which would endow the DNA nanotechnology with enhanced
capabilities and an extended scope of current and future applications. Two types of
FNAs, aptamers and DNAzymes, have been widely used in DNA nanotechnology.
In this chapter, we will first introduce these two types of FNAs, including what they
are, how they are obtained, and what their basic functions are. Then, the major part
will be focusing on current applications of these FNAs in DNA nanotechnology.

2.2 Functional Nucleic Acids (FNAs)

2.2.1 Aptamers

The name “aptamer,” derived from the Latin expression “aptus” (to fit) and the
Greek word “meros” (part), was first used to describe RNA molecules that bind to
a small organic dye [ 29 ]. Single-stranded DNA or RNA oligonucleotides that adopt
specific three-dimensional conformations for targeting distinct molecules have been
termed aptamers. Aptamers can strongly bind to their target molecules with high