OptimersTM

An Optimer™ is the name that we use to refer to the minimal functional portion of a parent aptamer.

Aptamer libraries often contain primer binding sites and extended regions of random (or partially randomised) nucleotides. Once an aptamer selection programme is completed (and the individual aptamer clones have been identified); these primer sequences and additional nucleotides are no-longer required. Removing these non-binding sequences serves two purposes;

  1. The shorter the end Aptamer, the more cost effective they are to produce (reduced synthesis costs and increased yields).
  2. Shorter aptamers have fewer potential folds. Reduced conformational dynamics generally leads to improved binding activity.

At Aptamer Group we are dedicated to providing the best service that we can. We believe that Optimer™ isolation is a key part of the programme, so this is included in our process as standard.

As with our monoclonal aptamer identification process; we use a functional binding assay to identify the minimal binding fragment (Optimer™), rather than predicting them based on bioinformatic analysis. We isolate these Optimers™ using our automated Minimal Aptamer Fragment Identification (MAFI) screening process.

Aptamer fragments are screened using the same assay format as their ‘parent aptamer’, and ranked based on their performance in the same functional binding assay. Each fragment is compared with the parent aptamer (orange trace). Fragments which retain their function (Optimers™, green traces) are further characterised. Non-functional sequences (red traces) are discarded.
Secondary structure predictions for a protein binding Optimer™ (left) and its parent aptamer (right), show a 55% reduction in length of the final product and a likely conserved structural motif.

Small molecule binding Optimers™ are isolated using a variation of the Minimal Aptamer Fragment Identification (MAFI) screening process. As with protein targeting Optimers ™, the end result is a more cost effective reagent.

Aptamer fragments are screened using the same assay format as their ‘parent aptamer’, and ranked based on their performance in the same functional binding assay. Each fragment is compared with the parent aptamer (orange trace). Fragments which retain their function (Optimers™, green traces) are further characterised. Non-functional sequences (red traces) are discarded.
Secondary structure predictions for a small molecule binding Optimer™ (left) and its parent aptamer (right), show a 58% reduction in length of the final product and a likely conserved structural motif.

As with the parent aptamer; the Optimers have been isolated with the end application in mind. At Aptamer Group, we have shown that our Optimers perform well in a variety of assay and application formats, including fluorescence ELISA-like assays, Biosensors and Aptamer Mediated Affinity Chromatography (AMAC).

Biosensors immobilised with either the parent aptamer (red) or the best performing Optimer™ (green) show a concentration dependent response to their small molecule target. In this case, the Optimer gives a greater response and has a higher apparent affinity than its parent aptamer.
Both parent aptamer (red) and the best performing Optimer™ (green) were also used in a fluorescence ELISA-like assay. Both show a clear concentration dependent response to their small molecule target. In this case, the Optimer gives a greater response and increased sensitivity, compared to its parent aptamer.