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Our Research | Alpha Anomeric

What We Do

Our Research | Alpha Anomeric

Alpha Anomeric was founded in February 2018 to develop and commercialize its new proprietary alpha anomeric bicyclo DNA platform in in-house development programs as well as in partnership with academia and industry.

Eliminating common side effects

All state-of-the-art oligonucleotide chemistries require a modification of the natural phosphodiester linkage found in DNA and RNA in order to prevent rapid degradation by nucleases that are present in all biological fluids. These modifications, however, lead to either dose limiting toxicity in the case of the phosphorothioates that interact with many blood proteins, or to low target affinity and efficacy in case of the PMOs that are uncharged. By using an alpha anomeric backbone sugar (natural DNA and RNA are beta anomers), we achieve nuclease resistance and high biostability even when we retain the natural phosphodiester backbone that nature employs.

Increasing specificity and efficacy

The Watson Crick base pairing mechanism allows for the design of highly specific compounds for interference with RNA, which are called oligonucleotides. To modulate a single type of RNA within a cell, the targeted region within that RNA needs to be of a minimal length of 15 base pairs, and the binding strength between the oligonucleotide and the target RNA should be such that only the full 15 mer is capable of RNA modulation, but not shorter fragments of it. With an elevation of the melting temperature of approximately 1.4°C per base pair, alpha anomeric bicyclo DNA has a perfect selectivity to guarantee maximal efficacy, minimal off target effects and off-titration of active drug.

Our Research

Alpha anomeric bicyclo DNA is a new DNA analog with unprecedented pharmacological properties. The incorporation of an alpha anomeric bicyclic sugar into the oligonucleotide backbone and a new linkage geometry (7’-5’ instead of 5’-3’) allowed the design and synthesis of new DNA scaffolds with very high biostability, low toxicity and high cellualar activity.

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