Aptamers as Therapeutic Agents: Has the Initial Euphoria Subsided?

Aptamers are synthetic DNA or RNA oligonucleotide ligands with great potential for therapeutic applications. A vast number of disease-related targets have been used to identify agonistic, antagonistic, or inhibitory aptamers, or aptamer-based targeting ligands. However, only a few aptamers have reached late-stage clinical trials so far and the commercial infrastructure is still far behind that of other therapeutic agents such as monoclonal antibodies. The desirable properties of aptamers such as selectivity, chemical flexibility, or cost-efficiency are faced by challenges, including a short half-life in vivo, immunogenicity, and entrapment in cellular organelles. Aptamer research is still in an early stage, and a deeper understanding of their structure, target interactions, and pharmacokinetics is necessary to catch up to the clinical market. In this review, we will discuss the benefits and limitations in the development of therapeutic aptamers, as well as the advances and future directions of aptamer research. The progress towards effective therapies seems to be slow, but it has not stopped and the best is yet to come.