What even is an aptamer?
Human DNA is made of two strands that coil around each other in a double helix. Each chain is made up of a number of bases that "pair up" with their complementary base.
An aptamer is a single strand that, instead of attaching to a different chain, rolls itself up into a tangle, a bit like a pair of headphones getting tied up in your pocket. Depending on which bases are attached to the chain, the aptamer rolls up into a different shape and can hold on to different molecules.
Our goal with Aptamer-Based Oxygen Transporters (ABOT) is to create an aptamer that can hold onto a heme molecule in a way that allows the heme to pick up and drop off oxygen.
Heme is the active molecule in the hemoglobin present in your red blood cells and is responsible for oxygen transport, but can also pick up other molecules (we’ll have to deal with that later).
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Date
5 May 2022
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Phase
Moonshot Ideation
How we evolve it
To make sure that our aptamers are tangling up in the right way and holding onto the right molecules, we’re going to use the same theory that led to humans in the first place: evolution. Evolution is the change in the characteristics over several generations. Natural selection is the mechanism in evolution that keeps the best and discards the rest.
We’re going to apply evolution to aptamers by letting them fold, giving them opportunities to attach onto heme and oxygen, and then eliminating those who didn’t hold on properly. We then clone all the aptamers that did a good job while inducing mutations to progress faster and then tangle, attach, and eliminate until we have aptamers that are performing as we want.
This process should take from a couple of days to a month. Once we have a good aptamer, we will sequence its DNA so we can make more of it later. This is what lets us make the evolution a one-off thing.
How we modify the aptamer to be stable
With the aptamer’s DNA at our fingertips, we’ll transcribe it’s information into a different form called Locked Nucleic Acid (LNA). This is very similar to DNA but protects the aptamer from being degraded by the body’s enzymes.
The last step after transcription is PEGylation, which is just the addition of polyethylene glycol (PEG) to the LNA, protecting our aptamers from filtration in the kidneys.
These two steps mean that ABOT can stay in the blood for weeks, instead of 10-20 hours as seen in past synthetic oxygen transporters.
Manufacturing
At this point in the process, we have a blueprint on how to produce ABOT. There are now many possible paths for manufacturing and scalability. The best case is a new form of PCR that allows us to very cheaply produce insane amounts of DNA and LNA, bringing the price of ABOT to below $100. There is reason to believe this is possible since some variations of the enzymes used in PCR are able to unreliably incorporate LNA.
After manufacturing, we will partner with organizations like hospitals and Blood Services Canada to distribute these blood substitutes to those in need.
Hopefully, this has given you a better understanding of how our ABOT solution works. If you have any questions, feel free to reach out to us on LinkedIn (about the team page).