Commercializing aptamers in diagnostics (Part 1)

The first transcontinental railway in Canada had to make it through the rocky mountains. In the Kicking Horse Pass the grade was so steep that trains were at constant risk of derailing. This was solved with the introduction of a spiral tunnel through the mountain to reduce the grade. These spiral tunnels are still in use today.

I have often told clients that identifying an aptamer is like first seeing the mountains. It is exciting, we can watch the sun rise and set on the mountain, the snow accumulate in winter and melt in spring. But to commercialize an aptamer requires that we stop gazing at the mountain and actually climb over it. To discover a good aptamer is easy compared to succeeding in bringing it across the finish line of commercialization. We learned ourselves from scratch with our series of commercial aptamers for mycotoxin detection. It took us at least two years to move from discovering aptamers for ochratoxin A and aflatoxin B1 to develop these into commercial products.

Development of a commercial product requires a different set of problem solving skills than developing aptamers. Here is an overview of the problems to be faced.

• Obtain the limit of detection required for commercial relevance
  1. Reduce noise, increase signal
  2. Characterize specificity, and determine salt concentrations to maximize
• Characterize response over a relevant range of concentrations
  1. Is there a Hook effect? (high concentrations start to show low results)
  2. Where does linearity of response start to fail
• Demonstrate reproducibility in your own lab
  1. Test different formulations of the same test
  2. Test after storage for varying time periods
• Characterize and improve the robustness of the assay
  1. What can be varied, how much, and what components have to be carefully monitored
  2. Write a detailed Standard Operating Procedure (SOP)
• Transfer the technology to another party and have them reproduce your results
  1. Figure out why they are not… and fix the problem
• Develop a prototype for commercial scale
  1. Optimize the balance between ease of use, cost of production and performance

After all of these steps you are ready for regulatory approval and commercial scaleup. The way I see this process is that there is a solution space but it is nested in a large space of problems. It is necessary to design development experiments so that will tell you what direction you need to go in to improve things further. Finding out what works and what does not work is a start but it is not sufficient.

Publishing a paper demonstrating the affinity and specificity of a new aptamer is great, but this is like seeing a mountain for the first time. Developing that aptamer into a commercial product involves planning the path up the mountain, learning to adapt or change your path based on cliffs that were steeper than anticipated or rocks that were looser than they looked. With each aptamer we develop we learn in excruciating detail about a specific mountain, but we also learn about mountains in general. Mountain climbing and commercial development of aptamers is difficult, but both are more rewarding than gazing at something beautiful.