What is an aptamer?
Aptamers are oligonucleotides, single stranded DNA or RNA that mimic antibodies in their ability to bind to target molecules. Aptamers contain random regions internally, usually 40 nucleotides in length. Each aptamer sequence wants to be as double stranded as possible, and in order to achieve this, each sequence forms a different shape. The location of the charged nucleotides in space within each aptamer have the potential to fit against opposite charges on target molecules such as aptamers for proteins, or aptamers for metabolites or aptamers for drugs.
Aptamers are synthesized chemically, and the selection of aptamers for binding to target molecules takes place on the lab bench. We reward each aptamer that binds to a target molecule through a designed selection process (such as SELEX, or our proprietary method called FRELEX, which we will explain in another post) which results in those aptamers that bind with high affinity and high specificity being PCR amplified. The SELEX or FRELEX process is repeated several times in order to enrich aptamers that bind to the desired target and to remove aptamers that bind to closely related targets
All types of target molecules can be used for aptamer selection. Traditional SELEX aptamer selection can be used with proteins and peptides, our FRELEX method can be used to select small molecules such as drugs or metabolites, without a need to conjugate the molecule to a larger one to improve its antigenicity. This extends the range of aptamers to smaller molecules than are possible with antibodies. We also routinely use combinations of SELEX, FRELEX and cell SELEX to select aptamers that will bind specifically to transmembrane proteins (primarily receptors) on the surface of cells. This extends the range of aptamers on the large scale to targets that are also impossible for antibodies.
How is the development of an aptamer different from that of an antibody? Antibodies are proteins produced by animals as a response to the presence of foreign molecules. Antibodies have hypervariable regions that form different sequences in different cells. When a cell produces an antibody that succeeds in binding to a foreign target that cell is rewarded, and more of that antibody is produced. Other than that, aptamers are generally the same as antibodies in regard to their ability to bind to proteins, metabolites or drugs.
The ability of aptamers to mimic antibodies means that aptamers can be substituted for antibodies in a wide variety of applications including lateral flow devices, ELISA, biosensors, lab on a chip, electronic sensors as well as direct fluorescently labeled probes. Aptamers can also be readily conjugated to gold nanoparticles or quantum dots as a basis for point of care diagnostics.