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Diagram of aptamer shape fluctuation

Aptamer Design

The shape of an aptamer is very important for its binding affinity to the target. This is because the shape allows it to ‘fit’ into a target, but also orients the nucleotides involved in binding in a way that optimizes binding interactions. For aptamers to be developed for commercial products they need to constantly be in the ideal ‘shape’ for effective binding. This means that there is a need for optimization.

 

Optimization is needed because even though aptamers are always represented in one shape confirmation, their shape is actually constantly fluctuating at room temperature. This can create a problem because if the aptamer is in an unfavorable binding shape when it contacts a target, it will not bind. To improve binding, the aptamer needs to be in the shape that enables binding as often as possible. We use computer modeling of predicted secondary structures in flux as the basis for aptamer truncation and optimization. 

 

Diagram of aptamer shape fluctuation

 

With our in-silico modeling approach we routinely increase target binding affinity and specificity of sequences from their selected full-length forms to shorter sequences. The ability of NeoVentures to use aptamer energy landscapes to optimize performance is a crucial ingredient in the development of aptamers that can be commercialized. 

 

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