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B. Liu et al.
5.4.1 Strengthen Fundamental Research
The flexibility, namely the structural instability, of single-stranded nucleic acids
results in the unsatisfactory stability and repeatability of aptamer-based experiments in varied conditions. The conformation of aptamers is sensitive to many
parameters such as pH, temperature, and ionic strength, etc. Different intermolecular and intramolecular functional groups can interact with aptamers as well, and
consequently interrupt their function.
To conquer this problem, first, appropriate methods to characterize the structure
of aptamer are eagerly to be developed. The commonly used structural research
methods, no matter nuclear magnetic resonance, crystal diffraction, or cryo-electron
microscopy, are not always easily accessible for studying the structure of the aptamer.
Additionally, there is also a lack of methods to real-time observe the conformational
changes of the aptamer in solution/colloidal systems. The lack of knowledge of the
structure of the aptamer restricts the computer-aided simulation of the aptamer, as
well as the understanding of the functional mechanism of the aptamer. The further
understanding of the aptamer to a certain extent depends on the progress of structural
characterization methods.
Second, the aptamer applied in a medical device may need to be screened from
SELEX, which is conducted in the simulated real medical condition. So far, most
aptamers have been screened from SELEX under a specific pH, temperature, and
ionic strength. However, they will be possibly ineffective when the condition changes.
Screening strategies based on the application scenario might solve this problem,
notwithstanding the challenge to the SELEX technology.
Third, it is important to understand mechanisms of the interaction between
aptamers and their targets. This should be helpful in the following aspects: to obtain
the aptamer with higher affinity and specificity, so as to reduce the influence of
external environment on the specific binding; to narrow the scope of the candidate nucleic acid library through the computer-aided primary screening, thus greatly
reduce the screening workload; to adopt appropriate detection methods and signal
amplification strategies on the basis of aptamer structure and identification of recognition sites. A bold assumption is that, based on the sufficient research, it is possible to
determine the sequence of aptamers directly by rational design according to specific
needs.
5.4.2 Learn from Antibodies
It has been merely around 30 years since the debut of aptamers. Although its specific
binding properties to the targets are similar to those of antibodies, the aptamer is still
in its infancy compared to the over-100-year mature antibody. Many teething problems need to be overcome before aptamers eclipse the halo of antibodies, especially
B. Liu et al.
5.4.1 Strengthen Fundamental Research
The flexibility, namely the structural instability, of single-stranded nucleic acids
results in the unsatisfactory stability and repeatability of aptamer-based experiments in varied conditions. The conformation of aptamers is sensitive to many
parameters such as pH, temperature, and ionic strength, etc. Different intermolecular and intramolecular functional groups can interact with aptamers as well, and
consequently interrupt their function.
To conquer this problem, first, appropriate methods to characterize the structure
of aptamer are eagerly to be developed. The commonly used structural research
methods, no matter nuclear magnetic resonance, crystal diffraction, or cryo-electron
microscopy, are not always easily accessible for studying the structure of the aptamer.
Additionally, there is also a lack of methods to real-time observe the conformational
changes of the aptamer in solution/colloidal systems. The lack of knowledge of the
structure of the aptamer restricts the computer-aided simulation of the aptamer, as
well as the understanding of the functional mechanism of the aptamer. The further
understanding of the aptamer to a certain extent depends on the progress of structural
characterization methods.
Second, the aptamer applied in a medical device may need to be screened from
SELEX, which is conducted in the simulated real medical condition. So far, most
aptamers have been screened from SELEX under a specific pH, temperature, and
ionic strength. However, they will be possibly ineffective when the condition changes.
Screening strategies based on the application scenario might solve this problem,
notwithstanding the challenge to the SELEX technology.
Third, it is important to understand mechanisms of the interaction between
aptamers and their targets. This should be helpful in the following aspects: to obtain
the aptamer with higher affinity and specificity, so as to reduce the influence of
external environment on the specific binding; to narrow the scope of the candidate nucleic acid library through the computer-aided primary screening, thus greatly
reduce the screening workload; to adopt appropriate detection methods and signal
amplification strategies on the basis of aptamer structure and identification of recognition sites. A bold assumption is that, based on the sufficient research, it is possible to
determine the sequence of aptamers directly by rational design according to specific
needs.
5.4.2 Learn from Antibodies
It has been merely around 30 years since the debut of aptamers. Although its specific
binding properties to the targets are similar to those of antibodies, the aptamer is still
in its infancy compared to the over-100-year mature antibody. Many teething problems need to be overcome before aptamers eclipse the halo of antibodies, especially