Technology

Technology

TagCyx focuses on identifying novel nucleic acid based drugs for therapeutic applications. TagCyx has established an innovative nucleic acid-based drug discovery platform, the “Xenoligo™ system”. It enables screening of drug candidates from diverse oligonucleotide libraries containing the highly functional “fifth base”, and stabilizing molecules using our proprietary technology. The selected Xenoligo™ molecules express high selectivity and affinity against their targets providing some significant advantages compared to conventional aptamers, small molecules and protein therapeutics.

Innnovative Xenoligo™ drug discovery platform using proprietary genetic alphabet expanded SELEX system

Highly functional Xenoligo™ molecules are generated by a modified SELEX method, which includes repeated cycles of selection and PCR amplification. The DNA library, containing the fifth base (Ds base) in addition to naturally exisiting nucleic acids, Adenine, Thymine, Guanine and Cytocyne is the key of XenoligoTM generating diverse molecules consisting of of 1014 to 1015 size library. The hydrophobicity of the Ds base enhances the interaction with hydrophobic regions of the target molecules. Using only Ds, not using pairing partner of Ds, increases the structural diversity of each oligonucleotide in the DNA. After several rounds of the selection, final DNA mixture is identified by sequencer. Among them, the most strongly binding DNA oligonucleotide is optimized by a second doped SELEX, and remodeled by a proprietary method to generate Xenoligo™ which possesses increased thermal stability and nuclease resistance.

Key Advangages of Xenoligo™

  • High affinity and high selectivity to target molecules, at subpico moler order.
  • Synthesized chemically entirely without the use of host animals nor celluar systems.
  • High reproducibility of Xenoligo™ because of chemical synthesis
  • Inexpensive and reproducible production of Xenoligo™ by PCR

References

  • M. Kimoto, Mana Nakamura and I. Hirao, “Post-ExSELEX stabilization of un unnatural-base DNA aptamers targeting VEGF165 toward pharmaceutical applications,” Nucleic Acids Research., 44 (2016) 7487-7494
  • K. Matsunaga, M. Kimoto, Hanson C, Sanford M, Young HA,, and I. Hirao, “Architecture of high-affinity unnatural-base DNA aptamers toward pharmaceutical applications,” Scientific Reports., 5 (2015) 18478
  • M. Kimoto, R. Yamashige, K. Matsunaga, S. Yokoyama, and I. Hirao, “Generation of High-Affinity DNA Aptamers using an Expanded Genetic Alphabet,” Nat. Biotechnol., 31 (2013) 453-457.
  • Yamashige, M. Kimoto, Y. Takezawa, A. Sato, T. Mitsui, S. Yokoyama, and I. Hirao, “Highly specific Unnatural Base Pair Systems as a Third Base Pair for PCR Amplification,” Nucleic Acids Res., 40 (2012) 2793-2806

“Xenoligo™” is registered trademark by TagCyx.