Aptamers are short nucleic acids that bind to defined targets with high affinity and specificity. The first aptamers have been selected about two decades ago by an in vitro process named SELEX (systematic evolution of ligands by exponential enrichment). Since then, numerous aptamers with specificities for a variety of targets from small molecules to proteins or even whole cells have been selected. Their applications range from biosensing and diagnostics to therapy and target-oriented drug delivery. More recently, selections using complex targets such as live cells have become feasible. This paper summarizes progress in cell-SELEX techniques and highlights recent developments, particularly in the field of medically relevant aptamers with a focus on therapeutic and drug-delivery applications. 1. Introduction Aptamers are short nucleic acids (typically 12–80 nucleotides long) capable of specific and tight binding to their target molecules. The term aptamer is derived from the Latin word aptus (fitting) and the Greek word meros (part). Aptamers are selected by a process called SELEX (systematic evolution of ligands by exponential enrichment), which was established independently by Ellington and Szostak [1], Tuerk and Gold [2], and Robertson and Joyce [3] in 1990. A typical SELEX experiment starts with a library of up to 1015 random oligonucleotides, which can be DNA, RNA, or modified RNA (e.g., 2′-OMe or 2′-F). Some members of this enormous library are anticipated to bind a desired target. The key step of the SELEX procedure is to efficiently separate those few from the nonbinding species. Selected nucleic acids are then amplified and used for further selection rounds. A successful SELEX experiment will usually result in a collection of aptamers, which can subsequently be cloned and tested individually for their binding properties. The possible aptamer targets show a great diversity ranging from small molecules, like organic dyes [4], amino acids [5] or antibiotics [6], peptides [7], proteins [8], and viruses [9] to whole cells [10]. The dissociation constants ( values) of aptamer-target complexes are comparable to those of antibodies and can reach the picomolar range. In addition, aptamers exhibit the following interesting features, which set them apart from antibodies: they are selected entirely in vitro, their synthesis has been automated, and they can easily be chemically modified [11]. Furthermore, they can be stored and shipped without problems, because the stability of DNA aptamers, in particular, is almost infinite. Importantly, they are not
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