Re-entering the cell: Is the intracellular space the true therapeutic niche for aptamers?

First conceptualized in the early 1990s by the Tuerk, Gold, and Szostak laboratories, nucleic acid aptamers—often dubbed “chemical antibodies”—were envisioned as a disruptive class of targeted therapeutics.1 Selected via systemic evolution of ligands by exponential enrichment (SELEX), an iterative in vitro process that sorts massive combinatorial libraries for high-affinity sequences, aptamers fold into distinct tertiary structures capable of binding to protein targets with nanomolar or sub-nanomolar dissociation constants.