Biomedical Engineering Reference
In-Depth Information
a good template for patterning other molecules, studying biological molecular
interactions in nanoscale precision, sensing with unique properties, serving as
selective drug delivery vehicle, as well as driving the motion of nanodevices.
2.3.1
DNA Assembly with FNAs for Patterning
Due to the well-characterized and predictable conformation, DNA nanostructures
with encoded target sites on nanoscale precision imply that they provide a versatile
template for constructing nanoscale patterning. One promising application is to
direct the assembly of other components, like proteins. Since all natural biochemical
reactions occur at nanoscale regime, the assembly of proteins with nanoscale-
precision control is of great significance to mimic the biological procedures and
explore the fundamental biomolecular interactions.
Taking the advantage of precise spatial control of DNA nanostructures,
various strategies have been adopted to localize proteins on DNA nanostructures.
Streptavidin-biotin interaction has been widely used by modifying DNA
oligonucleotides with biotin and fusing proteins with streptavidin [
61
,
62
]. However,
the tedious modifying process and potential loss of protein function during the
fusion hindered its further development. Other strategies, such as specific antigen-
antibody interactions [
63
] and covalent linkage of proteins to nucleic acids by
crosslinkers [
64
,
65
], also encountered similar problems. Alternatively, aptamers
provide a robust platform to assemble proteins on DNA nanostructures with the
following advantages. First, as single-stranded DNA, aptamers could be easily
mounted on the DNA nanostructures and act as the addressable spots for proteins.
Second, theoretically, it is possible to generate aptamers against any targets of
interest with high affinity and specificity. Therefore, unlimited protein-aptamer
pairs could be applied on DNA nanostructures, and multiple proteins might also be
able to be patterned on the same structure with well-defined distance. Third, the
targets for aptamers are not just limited to proteins but can be extended to other
types of ligands.
To construct one-dimensional (1D) patterning, single- or double-stranded DNA
is already an excellent template. Several strategies have been adopted to build the
lengthy nanostructures from ssDNA or dsDNA with aptamer periodically arranged
from patterning. For instance, rolling-circle amplification (RCA) is a technique
that a circular oligonucleotide sequence serves as a template for polymerization
amplification to generate a long complementary ssDNA with periodic repeats [
66
].
Willner's group applied RCA strategy to create linear DNA chains containing
aptamers for self-assembly of 1D periodic protein-DNA composites [
67
]. As shown
in Fig.
2.2
a, the complementary sequences of aptamers have been encoded into
the circular template. After RCA reaction, a linear chain with periodic aptamer
sequences has been generated, and the aptamers on the linear chain can still
function to recognize their target proteins. By encoding single or multiple aptamer
complementary sequences in circular template, linear chains with single or multiple
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