Covalent DNA aptamer: a long-acting but detoxifying drug modality

Middle-sized biological molecules (e.g., peptides, nucleic acids), namely ‘aptamers’, are utilized to inhibit disease-related target proteins. Aptamers are recognized as promising future drug modalities, because the target recognition is usually so stringent that can avoid unwanted side-effects. A major obstacle of a conventional aptamer for drug use is that they are not long-acting (A: known fact). The aptamer cannot bind to the target eternally; it will be released from the target eventually. Plus, the unbound aptamer tends to be degraded in serum, which contains many peptidases/nucleases. 
To overcome these problems, we have recently developed ‘covalent’ aptamers. A covalent bond between the aptamer and the target causes semi-permanent drug action. Plus, serum resistance of a DNA-type (B: this work) or peptide-type covalent aptamer (our previous work) is observed; the covalently-bound aptamer is protected against various nucleases/peptidases in serum and remains stable. 
The semi-permanent inhibition by a covalent aptamer may lead to unexpected long-acting side-effects or a too-strong medicinal effect. In the case for the DNA aptamer, one can also detoxify the drug effect at any time by introducing a complementary DNA strand as an antidote (B: this work), which eventually destructs the aptamer's 3D structure and the aptamer becomes susceptible again to the nuclease-mediated degradation.