14 Perspectives of Aptamers for Medical Applications
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difficult to generate antibodies against. To some extent, the aptamer can make up an
insufficient antibody, which is normally difficult to achieve.
Aptamers are selected in vitro, which overcome the limitations of the need for
cell lines or animals, they present no immunogenicities compared with antibodies,
the immunogenicity of antibody is a huge hinder for its clinical application. The
aptamer can be selected by optimizing and expanding the diversity of the library,
which dramatically enhanced the specificity and biostability of nucleic acid aptamers
to acquire both lower dissociation rate for target molecules and suitable binding
affinities.
Aptamer screening is efficient and cost effective. Once selected, aptamer can be
synthesized with high reproducibility and purity in a large quantity and automated
production of aptamers with low batch-to-batch variations. This trait is uneasy for
antibodies to achieve batch stability.
Except that, as a nucleic acid, the aptamer can be modified and bioconjugated
while retaining the affinity with various functional elements, such as fluorophores,
nanoparticles, or enzymes. The aptamer can also tag with fluorogenic or radioisotope
reporters or even conjugated with therapeutic agents as efficient target therapy tools
in the clinical scenario [5]. Most importantly, the modification or bioconjugation
of aptamer can be conducted automatically on a DNA/RNA synthesizer or can be
achieved under biofriendly conditions of the aptamer.
Another unparalleled advantage of the aptamer is its stability in working solution; the chemical structure of aptamer was so simple that it could trigger full
conformational recovery even after thermal or chemical denaturation, it can keep
in room temperature and owns a long shelf life, which is definitely not the case for
proteinaceous antibody.
All the above-mentioned merits of aptamers make them widely used in various
biomedical scenarios, including in vitro bioanalysis, in vitro diagnostics (IVD),
bioimaging, biomarker discovery or identification, aptamer-aided drug discovery,
and targeted therapy.
Unfortunately, most aptamer applications and studies are still on the bench, and
a limited aptamer enters the clinical trial. What affects the effective transformation
of aptamers from the laboratory to the clinic?
14.2.2 Demerits
Molecular size is a double sword for aptamer. On the one hand, it endows the aptamer
excellent penetrating effects to deliver the drug to the target cells, and it seems to
bring a bright future in targeted therapeutic; on the other hand, kidneys are likely to
rapidly eliminate the substances with a molecular weight <50 kDa [6]. Most aptamers
are prone to an efficient renal clearance due to their rather small size (5–15 kDa).
Like any natural oligonucleotides, aptamers are prone to rapidly degrade by nucleases in biological media, especially in the blood. It is a serious problem that puts
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difficult to generate antibodies against. To some extent, the aptamer can make up an
insufficient antibody, which is normally difficult to achieve.
Aptamers are selected in vitro, which overcome the limitations of the need for
cell lines or animals, they present no immunogenicities compared with antibodies,
the immunogenicity of antibody is a huge hinder for its clinical application. The
aptamer can be selected by optimizing and expanding the diversity of the library,
which dramatically enhanced the specificity and biostability of nucleic acid aptamers
to acquire both lower dissociation rate for target molecules and suitable binding
affinities.
Aptamer screening is efficient and cost effective. Once selected, aptamer can be
synthesized with high reproducibility and purity in a large quantity and automated
production of aptamers with low batch-to-batch variations. This trait is uneasy for
antibodies to achieve batch stability.
Except that, as a nucleic acid, the aptamer can be modified and bioconjugated
while retaining the affinity with various functional elements, such as fluorophores,
nanoparticles, or enzymes. The aptamer can also tag with fluorogenic or radioisotope
reporters or even conjugated with therapeutic agents as efficient target therapy tools
in the clinical scenario [5]. Most importantly, the modification or bioconjugation
of aptamer can be conducted automatically on a DNA/RNA synthesizer or can be
achieved under biofriendly conditions of the aptamer.
Another unparalleled advantage of the aptamer is its stability in working solution; the chemical structure of aptamer was so simple that it could trigger full
conformational recovery even after thermal or chemical denaturation, it can keep
in room temperature and owns a long shelf life, which is definitely not the case for
proteinaceous antibody.
All the above-mentioned merits of aptamers make them widely used in various
biomedical scenarios, including in vitro bioanalysis, in vitro diagnostics (IVD),
bioimaging, biomarker discovery or identification, aptamer-aided drug discovery,
and targeted therapy.
Unfortunately, most aptamer applications and studies are still on the bench, and
a limited aptamer enters the clinical trial. What affects the effective transformation
of aptamers from the laboratory to the clinic?
14.2.2 Demerits
Molecular size is a double sword for aptamer. On the one hand, it endows the aptamer
excellent penetrating effects to deliver the drug to the target cells, and it seems to
bring a bright future in targeted therapeutic; on the other hand, kidneys are likely to
rapidly eliminate the substances with a molecular weight <50 kDa [6]. Most aptamers
are prone to an efficient renal clearance due to their rather small size (5–15 kDa).
Like any natural oligonucleotides, aptamers are prone to rapidly degrade by nucleases in biological media, especially in the blood. It is a serious problem that puts