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Optimized Aptamers

For aptamers to be able to compete with antibodies in health care applications they need to perform as well as antibodies. At NeoVentures we have considered how antibodies evolve in response to an antigen and we have applied a similar approach to the optimization of aptamers.

The presentation of an antigen to an immune system is analogous to SELEX selection of aptamers against the same antigen. With immunity, the naïve antibody repertoire (library) is screened for potential antibodies that bind to the antigen. In SELEX a naïve library of aptamer sequences is screened for those that can bind to the same antigen. To this point the two processes are the same, except that one takes place inside a body and the other in test tubes. The next step for the immune system represents an advantage for antibodies. Successful antibodies from the selection process undergo an intense selection process for further improvement through mutation and recombination, then the very best of these are amplified and retained for immune response. For aptamers to compete with antibodies we need to introduce this second refined selection step.

I like to think about the initial naïve antibody or aptamer library as representing the stars in the night sky. The whole sky represents all the possible solutions, the naïve libraries represent those solutions that we have to start with. In both systems, the identification of a star serves as a guide to explore the space around that star more intensely. It is probable that there are sequences near the star that will perform much better than the star itself.

For aptamers we can refine the search to an in-silico process. Over the past few years the software for predicting the secondary and tertiary structure of the aptamer sequences has improved considerably. I will describe exactly how we use this knowledge to improve aptamer performance in another blog, for this blog I just wanted to introduce you to the concept that this step is necessary in order to obtain aptamers that can perform similarly to antibodies, and that at NeoVentures this step is included as an essential element of every aptamer development project. We are only interested in providing our clients with aptamers that will support commercially viable product concepts, we are not interested in proof of concept. We want to support your development of aptamer based commercial products. This means we needed to develop the capacity to develop aptamers that can compete with antibodies in terms of performance.