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The Advantage of shorter Aptamers

“A person is a person no matter how small” Dr. Seuss in Horton’s Hears a Who

I am not sure how well distributed Dr. Seuss books are outside of North America. They were a staple of my childhood, and I made sure that they were a staple of my children’s childhood. I have also used this quote in the reverse sense, “A person is a person, no matter how big” when psyching myself for meetings with big companies. What does this have to do with aptamers? The length of an aptamer is not a function of its size but it’s ability to bind to a target molecule.

We use 80 nucleotide sequences in our aptamer selection process, with a random region of 40 nucleotides. This is a good size for selection because the relatively large random region results in the majority of the secondary structure not being involved with the primer recognition sequences. An 80 nucleotide aptamer is not desirable for commercial application however.

  • The extra nucleotides on a longer aptamer are not involved in the binding event and can reduce both the rate of complex formation by getting in the way, and the rate of complexes coming apart by reducing the stability of the aptamer structure.
  • In the synthesis process for an aptamer there is failure to appropriate add the next nucleotide approximately 0.8% of the time. The cost of aptamer synthesis is based on the cost of the components used to create it. The longer an aptamer is, the less actual aptamer you derive from the same amount of starting components

In the case of aptamers the optimum size is perhaps closer to Goldilocks than to Dr. Seuss, not larger or smaller than it needs to be.