The Future of Aptamers in Diagnostics – Part 1

Aptamers have not fulfilled the promise of significantly replacing antibodies as the basis for diagnosis, with very little in the way of commercial successes. NeoVentures Biotechnology Inc. was the first company globally to commercialize an aptamer in a diagnostic application with our series of aptamers for mycotoxins. We discontinued this product in order to focus on the needs of our clients however. Aptamers are being used commercially in in-house applications for product screening, quality control and affinity based purifications by several companies.

So, what has been the primary constraint to commercialization (certainly not lack of effort), and what does the future look like?

The primary difference between aptamers and antibodies lies in their selection systems. Antibodies are injected as free molecules into the blood stream where antibodies are developed against them as foreign antigens. This results in two major differences from aptamer selection.

The free form of proteins in the blood stream mean that the proteins are able to spontaneously dimerize with each other, to become loaded with cations, and are free from any folding constraints. The immobilization of proteins for aptamer selection means that the proteins are more likely to stay isolated, not only from each other but from other molecules that may interact with them in blood. We have observed some instances where aptamers bind to the immobilized recombinant protein but not to the free protein in a complex matrix.

Immune tolerance ensures that antibodies raised against foreign antigens do not bind to host proteins. Researchers have attempted to replicate this constraint in aptamer development by using counter-selection during SELEX. However, the underlying mathematics of SELEX-based counter-selection show that this approach cannot achieve the same level of specificity provided by immune tolerance.

Counter-selection effectively removes aptamers that strongly cross-react with off-target molecules, but it becomes progressively less effective at eliminating weak cross-reactivity. Because serum albumin is present in blood at an average concentration of approximately 600 µM, while many target molecules are present at around 600 pM, achieving adequate specificity requires a million-fold discrimination. SELEX cannot deliver this level of sensitivity, and neither can the use of modified nucleotides to enhance affinity.

NeoVentures Biotechnology has been developing aptamers for over twenty years. We are the only company that appears to have recognized these fundamental constraints and actively re-invented aptamer development to overcome them.

For inquiries, feedback, or further information, please don’t hesitate to reach out.

The NeoVentures Team.