Why consider aptamers for therapeutic applications? There has only been one aptamer based therapeutic ever approved, Macugen (https://en.wikipedia.org/wiki/Pegaptanib) and the commercial sales for this treatment were not blockbuster… The biggest issue facing any therapeutic development effort is definitely the risk of failure, especially the risk of failure late in development. So why should you consider aptamers when the success has been underwhelming to date?
There are actually several reasons.
- Aptamers are better now because of next generation sequence characterization and because of NeoVentures proprietary energy landscape optimization approach.
- Aptamers will not cause an adverse immune response. Blood contains an abundance of oligonucleotides already.
- Aptamers will be cleared through the renal system (pharmacokinetics are clear).
- Aptamer structures are easily manipulated.
This last point is I think actually the strongest of the four. When embarking on a therapeutic discovery project risk is reduced is you can work with a meaningful family of related therapeutic compounds. Given the identification of an aptamer that binds to your target of interest, it is trivial to create a family of aptamers with similar properties with simple nucleotide substitutions. In this way it is possible to dial up and down the level of effect of the therapeutic aptamer.
We are actively engaged in the use of molecular dynamics to model the structural interaction of aptamers with these targets. This is clearly the approach of the future for intelligent drug design and this will be achievable first with aptamers.
Aptamers have underwhelmed to date with therapeutic applications, but I would not bet against this underdog for the future. To discuss your potential application with experts at NeoVentures please contact us .