aptamer

An aptamer is a short, single-stranded nucleic acid molecule, either DNA or RNA, that can fold into intricate three-dimensional structures capable of binding with high affinity and specificity to a chosen target. Targets can include small molecules, proteins, whole cells, or even nanoparticles. Through shape complementarity and electrostatic interactions, aptamers can inhibit, activate, or alter the function of their targets, functioning similarly to antibodies but produced entirely by chemical synthesis.

Aptamers are identified through an in vitro selection process known as SELEX (Systematic Evolution of Ligands by Exponential Enrichment). A large library of random sequences is exposed to the target, and sequences that bind are isolated, amplified, and subjected to additional rounds of selection to enrich high-affinity binders. RNA aptamers are typically reverse-transcribed and amplified back to RNA, while DNA aptamers are amplified directly. Variants of SELEX exist to accommodate different targets, such as small molecules, cells, or whole proteins, and to enhance stability. Chemical modifications, including 2'-fluoro, 2'-O-methyl, or locked nucleic acids, improve nuclease resistance; Spiegelmers use L-ribose to resist degradation.

Applications of aptamers span therapeutics, diagnostics, and research tools. They serve as biosensors (aptasensors), diagnostic reagents, and targeted therapeutics or drug-delivery agents. Advantages over antibodies include synthetic production with high batch consistency, ease of modification, and potential for chemical stability. Challenges include susceptibility of RNA aptamers to nucleases, potential immunogenicity, and delivery to in vivo targets. The first approved aptamer drug, Pegaptanib (Macugen), entered the market in 2004 for age-related macular degeneration, illustrating the clinical potential of this technology.