Antibody Binding vs. Aptamer Binding
The immune system has developed very effective screening methods for eliminating antibodies that bind even weakly to self targets such as serum albumin and IgG. Aptamer selection is done outside the body, on the bench which provides many advantages but implicit immune tolerance in selection is not one of them.
Counter selection against off-targets has been the only way to produce aptamers that will not bind to other targets in bodily fluids. SELEX is based on the use of 1E15 sequences derived from 1.2E24 possible sequences. This means that every selection is based on a new set of sequences. It has not been possible to test the same starting set of sequences on different targets.
Counter selection is very effective against those sequences that bind tightly to the off target. It is not effective in removing those sequences that bind weakly. To be clear, counter selection is not as effective or as thorough as immune tolerance.
Does this really matter? Unfortunately, yes. Abundant proteins like serum albumin are present in blood at an average concentration of 600 uM. If we are trying to detect targets at much lower concentrations even weak counter-binding will result in saturation of aptamer binding to serum albumin.
NeoVentures has overcome this problem with our new Neomer aptamer selection method. The method involves application of an average of 1,000 copies of each of the same 4.29 billion sequences to every target. This means that we can identify all the sequences that bind even weakly to abundant proteins and remove them as candidates for your target. In essence we have created an in-silico alternative to avoiding self-recognition. This is a game changing innovation which will definitely lead to better performance of aptamers in diagnostic applications. Read more about Neomer in our blog.
To learn more about what this means for your ability to use aptamers to overcome problems in your diagnostic portfolio, contact our team today.
Dr. Gregory Penner academic training was a blend of very practical plant breeding theory combined with molecular biology. He has used this blend of biology and mathematics to first develop and lead a cereal biotechnology research team with the government of Canada and subsequently as a global research leader with Monsanto Inc. He has been a thought leader in aptamer development globally for the last twenty years as CEO and President of NeoVentures. He has led this company to financial stability without outside investment with an integrated approach to aptamer discovery and commercialization. In 2015, he co- founded a second company, NeoNeuro in Paris France, focused on an innovative approach to identify Aptamarkers for complex diseases.