The use of the traditional SELEX method for aptamer development has led to the identification of aptamers that bind to a wide diversity of targets. However, there has been limited success with aptamers in therapeutic and diagnostic applications.
A key advantage of aptamer development over antibody development is that it is performed in vitro outside of living systems. This is also a disadvantage because antibodies are screened after development for their capacity to bind, even weakly, to self-targets in blood. Traditional aptamer selection does not have this step. The capacity to screen by using counter selection is useful, but ultimately not sufficient because it does not effectively remove aptamers that bind weakly to self-targets.
Why is This a Problem?
Serum albumin is present in blood at a concentration of 600 uM. Most abundant biomarkers are present at concentrations ranging from fM to low nM. This means that for every target molecule present, there are millions, or billions, of serum albumin molecules also present. Even very weak binding to serum albumin will saturate the aptamer, leaving none left to bind to the target, even if the aptamers bind to the target with very high affinity.
Binding between ligands and receptors is often misunderstood. These are never fixed binding events. These are associations that are on and off in microseconds. Thus, binding should always be thought of as an equilibrium. As such the concentration of what a ligand is binding to is equally important to the strength of binding.
At NeoVentures, we have always been leaders in developing aptamers as commercial products. With our invention of the Neomer method of aptamer development we have not only overcome the traditional problem of aptamers lacking specificity, but we have done so in such a profound as to change the very basis of aptamer science.
This is a bold statement, but we now have the data to back it up. The Neomer method involves the use of a library of the same 4.29 billion sequences for every selection. We have replaced the need for reiterative cycles of selection in SELEX by starting with an average of 1,000 copies of each sequence in this library rather than 1. We can characterize the level of binding of a target molecule on all 4.29 billion sequences in a single selection round, followed by a clever trick we employ for NGS analysis. We have characterized the fingerprint of HSA and IgG on this library and are able to ensure that any sequence that binds to these proteins even weakly is removed as a candidate for your target molecule.
The Future of Aptamers
The power of this new approach should be apparent to anyone involved in diagnostics or therapeutics. This means that now we can:
- Identify aptamers that bind to the same epitope across proteins
- Identify aptamers that distinguish between different isoforms of a protein
- Coupled with our proprietary FRELEX platform, Neomers enables the definitive identification of soluble metabolites.
We want to share access to the Neomer platform as broadly as possible. Thus, while we now provide the platform as the basis for our fee-for-service business, we are also providing the Neomer library on a license basis. We will provide you with our library, you perform the selection yourself, even the NGS analysis and we will analyze your data against our database of protein and metabolite fingerprints on the same library and provide you with the results. We are doing this while maintaining our commitment to your ownership of the aptamers, royalty free.
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.