Aptamers Against Live Targets: Is In Vivo SELEX Finally Coming to the Edge?

Abstract

Targeted therapeutics underwent a revolution with the entry of monoclonal antibodies in the medical toolkit. Oligonucleotide aptamers form another family of target agents that have been lagging behind in reaching the clinical arena in spite of their potential clinical translation. Some of the reasons for this might be related to the challenge in identifying aptamers with optimal in vivo specificity, and the nature of their pharmacokinetics. Aptamers usually show exquisite specificity, but they are also molecules that display dynamic structures subject to changing environments. Temperature, ion atmosphere, pH, and other variables are factors that could determine the affinity and specificity of aptamers. Thus, it is important to tune the aptamer selection process to the conditions in which you want your final aptamer to function; ideally, for in vivo applications, aptamers should be selected in an in vivo-like system or, ultimately, in a whole in vivo organism. In this review we recapitulate the implementations in systematic evolution of ligands by exponential enrichment (SELEX) to obtain aptamers with the best in vivo activity.

Graphical Abstract

Abstract

Oligonucleotide aptamers can function as targeting therapeutics agents for many biomedical applications. However, their full potential has not yet been translated into the clinical arena. Selection conditions for an aptamer can play an important role in determining its final in vivo activity. In this review we summarize some of the main modifications and improvements in the selection methods that allow one to obtain better aptamers for in vivo targeting.