UK scientists have synthesised the world’s first artificial enzyme using nucleic acids produced in the lab called ‘XNA’. This research encourages the idea that life may evolve from material other than what scientists have long considered fundamental – RNA and DNA – and carries the field of synthetic biology closer to producing entirely new forms of life.
The instructions for building any living organism on Earth are contained in their genetic material, which is made from DNA and RNA. However, there is an alternative group of genetic building blocks called xeno nucleic acids (XNAs), which are artificial although carry the same information as DNA. XNA differs from typical DNA and RNA in that the five-carbon sugar group of each component nucleic acid has been replaced. Some of these replacements contain four carbon atoms, others as many as seven and one even contains a fluorine atom. Researcher Philipp Holliger from the Laboratory of Molecular Biology in Cambridge advised that their work with XNA shows that there is more to the fundamental imperative for life than DNA and RNA. Even with these replacements, XNA remains functionally and physically analogous to RNA by being able to fold into 3D structures and then ‘cut and paste’ specific nucleic acid sequences, however may still be unnatural and alien to humans.
Enzymes are biological catalysts, which are responsible for many metabolic processes that sustain life. The development of catalysis in early genetic polymers, such as RNA, is thought to have been a key step in the creation of life on Earth. Scientists have shown previously that RNA can itself act as an enzyme by folding into specific 3D structures and binding particular substrate. The ability of these synthetic XNAzymes with unconventional backbone chemistries to perform identical roles has profound implications on the conditions for the emergence of life, widening the boundaries for potential planets that might be capable of hosting life. The lead author of this study, Alex Taylor, said: “The [discovery] raises the possibility that, if there is life on other planets, it may have sprung up from an entirely different set of molecules, and it widens the possible number of planets that might be able to host life.”
XNAs have been synthesised for decades; the most compelling aspect of this study is the demonstration of what they may do, specifically replication and evolution. Pinheiro’s team designed specialised molecules that may synthesise XNA from a DNA template and then copy it back into the DNA – a system that replicates and propagates artificial genetic information, just like DNA and capable of evolution.
Furthermore, the XNAs have proven to be more robust than naturally occurring nucleic acids because XNAs are made in the lab. DNA and RNA may be forcibly evolved to bind a specific target however they are often unsuitable therapeutic agents because they are rapidly degraded down by nucleases in the body. XNA however, stays aloof from the human body’s natural enzymes and therefore remains intact. This property makes XNA an ideal candidate for long-term treatment of RNA-related conditions. According to Holliger, “It may be possible to design therapeutic XNA molecules that can cleave to an oncogene [cancer gene] or to viral RNA.”
These findings may have implications for biotherapeutics, nucleic acid treatments, exobiology and research into the origins of life itself. Little work might be needed to shape XNA molecules to bind specific therapeutic or diagnostic targets because it may be directly synthesised in a lab. Additionally, XNA molecules might, for example, be used to synthesise life forms, which may be sent into heavily polluted environments to clean up. This may be quite far in the future, nevertheless as the biological machinery designed to handle XNA develops, so too might synthetic systems be able to function on their own.
How might the production of a synthetic life form contest the paradigm of DNA- and RNA-based life?