Artificial DNA analogues can be used to speed up chemical reactions

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Research perspective written by Alexey S. Morgunov
MRC Laboratory of Molecular Biology
Cambridge, UK

How can I explain the importance of this research to the general public?

All life depends on chemical reactions that would occur too slowly without complex molecules capable of speeding them up (catalysts) and all life needs to be able to store a blueprint of itself in the form of genetic information. Although today there exist three chemistries that perform these functions — DNA and RNA for storing information, and RNA and proteins for catalysing reactions, it is believed that early life relied exclusively on RNA for both functions.

This study suggests that RNA is not unique and there are alternatives to natural molecules that can perform both functions critical for the emergence of life. Thus, the choice of RNA may have just been an accident of prehistoric chemistry, and this opens up the possibility that life elsewhere in the Universe could be based on chemistries different to our own.

In addition to this, the new molecules that the researchers generated, called XNAs, have the potential to be used in medical applications as they are more stable than their natural analogues, raising the possibility of bioactive drugs with increased efficiency and shelf-life.

Why is this important for researchers in fields other than molecular biology?

This study revealed that synthetic genetic polymers (XNAs) are capable of catalytic activity, which has implications for our understanding of emergence of life as it expands the chemical boundary conditions for polymers capable of heredity, evolution and now also catalysis — hallmarks previously only ascribed to RNA and DNA. The researchers also demonstrated methods for using directed evolution to generate new XNA species. As XNAs are more stable than RNA and less susceptible to nuclease digestion than either RNA or DNA, this technology can be of interest for generating nucleic acid analogues with binding or catalytic activities for pharmaceutical purposes.

Why is this important for researchers in the same field?

This study describes the directed evolution of synthetic genetic polymers (XNAs) with chemically modified backbones, which are capable of RNA endonuclease and ligase activity. Catalysis is demonstrated in four different chemistries (arabino nucleic acids, ANA; 2’-fluoroarabino nucleic acids, FANA; hexitol nucleic acids, HNA; and cyclohexene nucleic acids, CeNA). Additionally, the authors describe a FANA-FANA ligase metalloenzyme and present technologies for generating catalytically active polymers from non-natural chemistries. This study is the first to show that catalytic activity is not limited to natural biopolymers, expanding the spectrum of chemistries that can potentially sustain life.

Original article

Catalysts from synthetic genetic polymers
Alexander I. Taylor, Vitor B. Pinheiro, Matthew J. Smola, Alexey S. Morgunov, Sew Peak-Chew, Christopher Cozens, Kevin M. Weeks, Piet Herdewijn, Philipp Holliger
Nature, published online 1 December 2014

Acknowledgements

This work was supported by the UK Medical Research Council, the European Science Foundation, the Biotechnology and Biological Sciences Research Council UK, the European Union Framework, the European Research Council, the US National Science Foundation.The original text was published by Nature Publishing Group.