Xeno Nucleic Acids: from synthetic biology to precision medicines

‘Life on Earth uses a small chemistry set to make its genetic material, but is DNA (& RNA) the only “secret of life”? Synthetic biology is revealing that a multitude of artificial chemical analogues of DNA – “Xeno Nucleic Acids” (XNAs) – are capable of storing genes, replicating and evolving in the test tube. As well as their potential for creating alternative “xenobiology”, informing our understanding of the chemical origins of life and how we might look for life elsewhere in the cosmos, XNA molecules with properties beyond the natural biopolymers can be evolved to have sophisticated molecular functions we normally associate with proteins. Short XNAs could combine the specificity and mechanism of action of protein biologics with the chemical robustness, versatility and scalable synthesis of small molecule drugs – in principle, an entire pharmacopeia could be prepared using a common set of chemical building blocks as quickly and easily as we do a DNA primer for PCR. In this talk, I will describe our recent work investigating the potential for XNAs to fold into a variety of RNA-cleaving enzymes (“XNAzymes”) capable of targeting disease-associated RNA with single-nucleotide specificity.’