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J. Qu and J. Zhang
12.1 Introduction
Aptamers are single-stranded DNA or RNA nucleotides having a length of 40–100
mers. Recently, they also have been extended to small peptides with 10–30 amino acid
residues [1–3]. The name of aptamer originally comes from Latin “aptus”, which
means “fit” [4]. These single strands of nucleotides or peptides can specifically
recognize and bind to a great deal of target molecules, such as metal ions [5], organic
dyes and amino acids [6], antibodies [7], proteins [8], whole cells [9, 10], organs
[11], viruses and bacteria [12, 13], by various intermolecular forces, such as van
der Waals forces, hydrogen bonding, base stacking, etc. Aptamers are generally
selected by systematic evolution of ligands by exponential enrichment (SELEX),
and traditional SELEX is largely composed of two processes, including selecting
aptamers with affinity to targets and amplifying the bound aptamers [14–16]. During
the past 30 years, over 2000 aptamers have been developed against a wide variety of
targets [17, 18].
Aptamers are considered as “chemical antibodies” because of their similar functions between aptamers and classical antibodies [19]. Despite their similarity in
functions, aptamers have more advantages than classical antibodies such as long
half-life, small size, low or no toxicity, and low immunogenicity [20]. Due to these
merits, aptamers have attracted worldwide attention for the diagnosis and therapy of
various diseases such as cancer, inflammatory diseases, etc. [21–26]. Pegaptanib, also
called Macugen, is the first aptamer approved by the US Food and Drug Administration to treat ocular neovascularization in December 2004. Meanwhile, it represents a
milestone in drug development, because it is the first aptamer which is successfully
used as a therapeutic agent in human beings [27, 28]. Although pegaptanib is the
only approved aptamer, several aptamers are currently in clinical trials such as an
anti-Factor IXa aptamer [29] and an anti-von Willebrand Factor (vWF) aptamer [30].
Due to their high affinity and specificity, ability to block protein–protein interactions,
aptamers present a promising modality for addressing non-drugable targets.
Neurodegenerative disorders are a group of disorders that are characterized
by the progressive degeneration of neurons in the central nervous system such
as Alzheimer’s disease(AD), Parkinson’s disease (PD), Transmissible spongiform
encephalopathies (TSEs), and Huntington’s disease (HD) [31]. Nowadays, the prevalence of neurodegenerative diseases is increasing, partly owing to the extensions in
lifespan, but effective treatments are still lacking. These diseases are characterized
by neuronal dysfunction and death, and most of them are associated with the accumulation of misfolded proteins in the brain [32]. The protein aggregation process
involves misfolded proteins that become prone to self-association into small aggregates, which are sometimes called oligomers. Then, these aggregates can recruit
additional monomers and extend through fibrillar structures. The link between the
aggregation phenomena and neurodegeneration is generally poorly understood. For
each disease, it is not clear which species (such as the misfolded starting monomer, the
oligomer, or the final aggregation body) is toxic for neurons. Although the pathologic
mechanisms of these diseases are still elusive, much research progress has been made
J. Qu and J. Zhang
12.1 Introduction
Aptamers are single-stranded DNA or RNA nucleotides having a length of 40–100
mers. Recently, they also have been extended to small peptides with 10–30 amino acid
residues [1–3]. The name of aptamer originally comes from Latin “aptus”, which
means “fit” [4]. These single strands of nucleotides or peptides can specifically
recognize and bind to a great deal of target molecules, such as metal ions [5], organic
dyes and amino acids [6], antibodies [7], proteins [8], whole cells [9, 10], organs
[11], viruses and bacteria [12, 13], by various intermolecular forces, such as van
der Waals forces, hydrogen bonding, base stacking, etc. Aptamers are generally
selected by systematic evolution of ligands by exponential enrichment (SELEX),
and traditional SELEX is largely composed of two processes, including selecting
aptamers with affinity to targets and amplifying the bound aptamers [14–16]. During
the past 30 years, over 2000 aptamers have been developed against a wide variety of
targets [17, 18].
Aptamers are considered as “chemical antibodies” because of their similar functions between aptamers and classical antibodies [19]. Despite their similarity in
functions, aptamers have more advantages than classical antibodies such as long
half-life, small size, low or no toxicity, and low immunogenicity [20]. Due to these
merits, aptamers have attracted worldwide attention for the diagnosis and therapy of
various diseases such as cancer, inflammatory diseases, etc. [21–26]. Pegaptanib, also
called Macugen, is the first aptamer approved by the US Food and Drug Administration to treat ocular neovascularization in December 2004. Meanwhile, it represents a
milestone in drug development, because it is the first aptamer which is successfully
used as a therapeutic agent in human beings [27, 28]. Although pegaptanib is the
only approved aptamer, several aptamers are currently in clinical trials such as an
anti-Factor IXa aptamer [29] and an anti-von Willebrand Factor (vWF) aptamer [30].
Due to their high affinity and specificity, ability to block protein–protein interactions,
aptamers present a promising modality for addressing non-drugable targets.
Neurodegenerative disorders are a group of disorders that are characterized
by the progressive degeneration of neurons in the central nervous system such
as Alzheimer’s disease(AD), Parkinson’s disease (PD), Transmissible spongiform
encephalopathies (TSEs), and Huntington’s disease (HD) [31]. Nowadays, the prevalence of neurodegenerative diseases is increasing, partly owing to the extensions in
lifespan, but effective treatments are still lacking. These diseases are characterized
by neuronal dysfunction and death, and most of them are associated with the accumulation of misfolded proteins in the brain [32]. The protein aggregation process
involves misfolded proteins that become prone to self-association into small aggregates, which are sometimes called oligomers. Then, these aggregates can recruit
additional monomers and extend through fibrillar structures. The link between the
aggregation phenomena and neurodegeneration is generally poorly understood. For
each disease, it is not clear which species (such as the misfolded starting monomer, the
oligomer, or the final aggregation body) is toxic for neurons. Although the pathologic
mechanisms of these diseases are still elusive, much research progress has been made