Therapeutic oligonucleotides include a wide spectrum of molecules with different chemistries and functional properties such as antisense, RNA interference, immunorecognition and aptamer binding. While the idea of antisense oligonucleotides to specifically target single genes dates back to the 1970s, one of the most fascinating insights of recent years was that nature itself uses endogenous oligonucleotides for the regulation of gene function and control of cellular homeostasis on a large scale. Thus, like antibodies, oligonucleotides can be regarded as natural compounds that act through natural mechanisms.
The great advances in nucleic acid chemistry now allow it to make not only large quantities but also a large variety of molecules with distinctly unique and desirable properties. Together with changes of sequence and oligonucleotide design, the chemical space available for oligonucleotide development is enormous. Now with our recent insight in how nature uses oligonucleotides for the regulation of cellular functions and defense mechanisms, the therapeutic application of this class of molecules becomes much more straight forward. Consequently, the OTS covers therapeutic oligonucleotide development from research of basic principles to preclinical models and through clinical application.