TAGCyx focuses on identifying and developing novel nucleic acid-based drugs for therapeutic applications. TAGCyx has established an innovative nucleic acid-based drug discovery platform for making ‘Xenoligo™ molecules, the ‘Xenoligo™ platform’. It enables screening of drug candidates from three dimensionally highly diverse oligonucleotide libraries containing a ‘fifth base’, and employs proprietary technology to make the products reasonably stable. The selected Xenoligo™ molecules exhibit high selectivity and affinity for their targets, providing significant advantages compared to conventional aptamers, small molecules and other biologics.
Xenoligo™ molecules are generated by a modified SELEX method, which includes repeated cycles of selection and PCR amplification. The in vitro SELEX selection process – involving no cells or animals – allows the screening of extremely large and diverse DNA libraries of 1014 to 1015 molecules. The libraries contain a fifth base (Ds) in addition to the naturally existing nucleic acids, adenine, thymine, guanine and cytosine. A second unnatural base (Px) that pairs specifically with Ds allows the PCR amplification required for each round of SELEX. In the single-stranded, Ds-containing aptamers, the hydrophobicity of the Ds base enhances the interaction with hydrophobic regions of the target. After several rounds of selection, DNA mixture is analyzed by Next Generation DNA sequencing. The most strongly binding oligonucleotide is optimized by a second, doped SELEX, then remodeled by a proprietary method to generate the final Xenoligo™, which possesses greatly increased thermal stability and nuclease resistance.
The ability to incorporate a hydrophobic base solves a longstanding weakness of aptamer technology, allowing many more protein targets to be addressed and the affinities of the resulting interactions to be much greater.