Neomer Immune Tolerance
What is Immune Tolerance?
Immune Tolerance is in place in the body to make sure that our immune system does not react to our own cells, tissues, and organs. Autoimmune diseases occur when our immune system has lost tolerance and perceives everything as bad, even when it isn’t.
Immune tolerance is achieved when the immune system is developing lymphocytes (such as the B-cell in the figure right). Part of the process is to check to see if it binds to (recognizes) the antigen that is part of the ‘self’ (usually a sugar such as sialic acid or a part of a protein). If that cell recognizes the self antigen (even weakly), then it will trigger apoptosis, while those that do not recognize it will mature to be released in the body.
The Problem with SELEX
With traditional SELEX there is no way to account for self antigens like the body does.
SELEX follows a process of selecting for aptamers that bind to the target of interest, collecting the aptamers that bind to that target and then counter-selecting against the proteins that you do not want it to bind to. This works for removing sequences that bind strongly to the counter-target, but those that bind weakly will not be removed due to the washes involved in the procedure.
This creates a large problem in diagnostics, as sequences that bind weakly to off-targets that are naturally present in high abundance will saturate your aptamer away from your target, causing your sensitivity to decrease.
Another problem with SELEX is that each time a selection is started, a completely new library of sequences is used due to the sheer amount of possibilities that 40 random nucleotides creates. This means that you would need to select against every possible counter-target in the one selection because starting the counter-selection with a separate library is not possible. Therefore you cannot replicate the immune tolerance process that the body does.
How Neomers Changes Aptamer Science
Neomers overcomes all the problems SELEX has.
Due to the novel way that the library is designed, we are able to start with the same library for every selection. This allows us to complete selection on our target, as well as any off-targets separately. This means that it can be completed in one round, cutting the time of selection down significantly.
The sequences that bind to the targets and off-targets are then sent off for sequencing, Using this method, we are able to account for those sequences that bind to the off-targets, even those that bind weakly, and remove them from the list of potential sequences to be chosen if they also appear in our target binding sequencing results. Again, since this is all from the same library, we are constantly learning what sequences bind to certain targets.
We have already characterized the binding of our Neomer library to Human Serum Albumin (HSA), IgG, and other proteins found in high abundance in blood. This allows us to create an ‘immune tolerance’ system in-silico and remove any sequences that bind to a ‘self’ antigen.