Aptamers as promising agents in diagnostic and therapeutic applications

With increasing struggle to treat infectious diseases, for example due to multiple resistances against antibiotics, it becomes more and more important to develop new approaches in terms of therapy and diagnosis to allow an effective treatment. According to the world health organization especially carbapenem resistant Pseudomonas aeruginosa, Acinetobacter baumanii and Enterobacteriaceae like Klebsiella pneumonia or Escherichia coli are classified as critical [1]. A promising agent for the treatment and diagnosis of such pathogens are so called aptamers. The possible aptamer selection approaches and their application will be discussed throughout this chapter. The term aptamer is derived from the latin word “aptus”, meaning “to fit” and the greek word “meros”, which means “part”. Aptamers are short single stranded nucleic acids like ribonucleic acid (RNA) or deoxyribonucleic acid (DNA) and consist of up to 100 nucleotides. Through the formation of loops, stems and hairpins aptamers develop a three dimensional structure, which allows them to bind specifically to a certain target similar to an antibody [2]. However, aptamers have several advantages in comparison to antibodies making them a promising alternative for diagnostics and treatment. An outstanding advance of aptamers is their chemical and physical stability. While proteins are known to denature irreversibly at higher temperatures, aptamer reanneal to their original conformation and regain their ability to specifically bind to their target. For this reason aptamers are also stable during long term storage making them suitable for many applications. Furthermore, the identification and production of aptamers is more cost efficient. The identification and production of antibodies involves the immunization of animals and later big scale biotechnological fermentation for their recombinant production [3]. In addition to that, activity differences of the antibody may occur between individual batches making additional testing of each batch necessary. On the other hand, aptamers can be selected completely in vitro, even under non in vivo conditions, allowing the proper adjustment of the selected aptamer to the desired conditions depending on the desired purpose. The production of the aptamer is then achieved by synthesis by well-defined chemical reactions, making it highly reproducible and thus less differences in their activity appear. This also allows the modification of aptamers easily during the chemical synthesis. This modification can simply regard its stability but also fluorophores or other labels can be introduced to use aptamers as highly specific biosensors. Another important point is that antibodies usually exhibit a high immunogenicity. In contrast aptamers are much less immunogenic or toxic. For example a vascular epithelial growth factor (VEGF) specific aptamer has been reported, which can be given to monkeys at a 1000 fold higher dose than the necessary dose for treatment, detecting only a little immunogenic response [4,5]. Last but not least the generation of specific antibodies is limited due to the fact that they are normally gained through the immunization of animals. Consequently, the isolation of antibodies against toxic targets or molecules that trigger a high immune response is not practicable at all. Furthermore, it is not possible to find antibodies against very small targets which cannot be detected by the immune system. However, aptamers are selected in vitro, thus making the toxicity or immunogenicity of the target irrelevant and they are also able to bind very small targets like ions specifically.