The future of aptamers in diagnostics- Part 1

“The definition of insanity is doing the same thing over and over and expecting different results.” Albert Einstein-

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 being raised against foreign antigens do not bind to host proteins. This constraint has been mimicked in aptamer development through the use of counter selection with SELEX. Unfortunately, the mathematics of SELEX based counter selection demonstrate that it is not possible to obtain the same level of specificity as with immune tolerance. Counter selection works well to remove aptamers that cross-react strongly with other targets, it works progressively less well to remove aptamers that cross-react weakly. With serum albumin being present in blood at an average concentration of 600 uM, this means that if the target molecules concentration is 600 pM there is a need for a million fold sensitivity. SELEX cannot deliver this. Modified nucleotides to enhance affinity cannot deliver this.

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.