Biomedical Engineering Reference
In-Depth Information
3.1 Overview
3.1.1 What Is Aptamers?
DNA and RNA possess far broader applications than simply storing and transfer-
ring hereditary information. With the help of molecular engineering, powerful new
RNA and DNA molecules can be synthesized, which are capable of forming
complex three-dimensional structures, and possess surprisingly sophisticated
functions [
9
,
12
,
53
,
91
,
106
] in protein inhibition [
9
,
53
], reaction catalysis, and
gene regulation. These qualities make them potential therapeutic agents and tools
for exploring biological systems.
Among these engineered nucleic acids, aptamers are a group of short, structured
DNA or RNA molecules usually created through directed in vitro evolution, termed
SELEX: Systematic Evolution of Ligands by Exponential Enrichment [
23
,
110
].
Aptamers are called “synthetic” antibodies because they are designed specifically
to bind broad species of ligands with high affinities, from antibiotics [
94
,
108
,
126
],
vitamins [
123
], amino acids [
24
,
29
], to peptides [
4
], proteins [
67
,
118
] and
pathogen target [
20
,
54
,
58
]. However, aptamers possess many advantages over
antibodies. They are very small but can selectively recognize and bind specific
ligands with nano-molar or pico-molar ranges that match or exceed those of their true
antibody counterparts [
52
]. For example, the catalytic thrombin-binding aptamer
is only a 15-base sequence (Fig.
3.1a
)[
114
], but binds with nano-molar affinity [
10
].
In principle, aptamers can be generated against any target using in vitro methods that
are independent of animal, and are not limited by physiological conditions. Aptamer-
target interaction can be fine tuned by mutation, and all the sequences of current
aptamers have already been published. Aptamers are significantly more durable than
most protein receptors, yet simpler to synthesize, modify, and immobilize by low cost
methods. These advantages render aptamers great promise in bioanalysis [
30
,
31
,
40
,
41
,
48
,
105
], diagnostics [
13
], therapy [
121
], bio-catalysis and cell modulation [
109
].
3.1.2 Molecular Folding, Interaction and Biosensing
A highly specific, high-affinity interaction with its target is the most essential aptamer
property, which has ignited a variety of aptamer researches and applications.
Aptamers are much smaller, yet more flexible in structure. They must fold into
special structures upon binding with targets under specific conditions [
38
]. For
instance, aptamers for thrombin (Fig.
3.1a
) and HIV-1 Integrase should fold from
free chains into remarkably stable G-quartet forms in the presence of metal ions
[
16
,
20
,
56
,
57
,
90
,
114
,
115
]. More significantly, the G-quartet is common in areas
of the human genome such as telomeric DNA [
86
,
89
]. Thus, stabilization of the
G-quartet by interactions with small chemical reagents or ions could inhibit the
function of telomerase that is active in cancer cells [
32
]. Understanding the precise
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