The clear winner of our poll on antibody specificity was that antibodies have evolved to ignore HAS/IgG. I struggle with this, as I think it is too simple. Really, the way that antibodies rearrange to detect foreign antigens is open; there are no barriers to antibodies developing against self proteins. We probably should have used a different term than Chckpt Inb (checkpoint inhibition) as the second option, but this is the essence of why antibodies work well in matrices. Antibodies that develop to bind to self-targets within a biological matrix, such as human serum albumin or the Fc regions of IgG’s, undoubtedly do arise, but they are eliminated as dangerous. There are two systems, free – open development of antibodies against any target, and a counter-balancing system that detects and weeds out antibodies that bind to self proteins.
This counter balance system is what is missing from aptamer selection. We can perform counter selection against the matrix, but this only effectively eliminates those aptamers that bind really strongly to a matrix component. Counter selection against serum albumin should theoretically be performed at the concentration that serum albumin is present in blood (600 uM). We do this by using serum directly in counter selection with our FRELEX approach, or by immobilizing all of the protein in blood on UltraLink resin.
Our new Neomer selection platform represents the addition of a counter-balancing system to weed out all aptamers that bind, even weakly, to counter targets. With the Neomer system we are able to catalogue aptamer sequences that bind to dominant counter targets like HSA and IgG, and remove them as candidate sequences.
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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.