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• What is an Aptamer?
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Unlocking the Door to New Therapeutic Solutions

An aptamer is a nucleic acid macromolecule that binds tightly to a specific molecular target. Like all nucleic acids, a particular aptamer may be described by a linear sequence of nucleotides (A, U, T, C and G), typically 15-40 nucleotides long. In solution, the chain of nucleotides forms intramolecular interactions that fold the molecule into a complex three-dimensional shape. The shape of the aptamer allows it to bind tightly against the surface of its target molecule.

The term "aptamer" derives from the Latin aptus, "to fit", and was chosen to emphasize this lock-and-key relationship between aptamers and their binding partners. Because an extraordinary diversity of molecular shapes exist within the universe of all possible nucleotide sequences, aptamers may be obtained for a wide array of molecular targets, including virtually any class of protein, including enzymes, membrane proteins, viral proteins, cytokines and growth factors, and immunoglobulins. The Archemix pipeline includes aptamers directed to a wide range of validated therapeutic targets.

Selectivity and Affinity

Available high-resolution structural data suggests that the surface area of interaction between an aptamer and its molecular target is relatively large, so even small changes in the target molecule can disrupt aptamer association. Thus, aptamers can distinguish between closely related but non-identical members of a protein family, or between different functional or conformational states of the same protein. For example, an aptamer to basic fibroblast growth factor (bFGF) binds with greater than 1,000 fold selectivity to bFGF compared with other members of the FGF family.

In addition to exhibiting remarkable specificity, aptamers generally bind their targets with very high affinity. A survey of over 150 reported aptamers to a wide variety of targets reveals that the majority of anti-protein aptamers have equilibrium dissociation constants (K_ds) in the picomolar (pM) to low nanomolar (nM) range.