Aptamers Research Paper

Aptamers are chemically synthesized single stranded DNA or RNA sequences, ranging from 20 till 100 oligonucleotides. The term aptamer is derived from the Latin aptus, meaning ‘to fit,’ and the Greek meros, meaning ‘region’ [4]. Aptamers can be developed against a variety of targets for example, metal ions, proteins, cells, viruses and antibiotics. Because of their rather short structure they form stems, hairpins, loops and quadruplexes. These tertiary folding structures gives them an unique three-dimensional structure. Van der Waals forces, hydrogen bonding and electrostatic interactions allow these three-dimensional structures to bind their target with high affinity and specificity (Figure 1.1) [5], [6]. Therefore, aptamers are often referred

Compared with antibodies, aptamers are more advantageous. First of all, the production of antibodies is a long and expensive process. Whereas the chemical manufacturing process of aptamers is cheap and highly reproducible. Second, aptamers can be chemically modified at different sites with various functional groups while this site-specific modification is difficult to achieve in antibodies. Third, antibodies need to be handled in a stable system because of their irreversible denaturation. Unlike the conformational changes of aptamers, which are often reversible. Fourth, aptamers can target any molecules (from small ions to intact cells) through an in vitro process. In this method no mammalian cell systems are used, as is necessary in antibodies. Fifth, a large quantity can be made rapidly through a polymerase chain reaction. Other advantages as small size, fat tissue penetration and low immunogenicity allow to tolerate a broad range of conditions. Characteristic differences between aptamers and antibodies are summarized in Table 1.1.

Yet aptamers also have limitations. Basically it’s hard to predict the pharmacokinetics and other systemic properties. On the other hand their small size makes them susceptible to renal filtration, corresponding in a shorter half-life. As last, unmodified aptamers, especially RNA-based aptamers, are highly susceptible to nuclease degradation

An important parameter to describe the binding affinity of an aptamer is by the dissociation constant (Kd). Kd is an equilibrium constant that expresses the tendency of an aptamer and target to form a complex. It’s the aptamer concentration at which the concentration of target with aptamer bound equals the concentration of target without aptamer bound. So, a low Kd indicates a stronger binding between aptamer and its target. The Kd can be described by Equation 1