XNA or synthetic DNA, novel life forms?

The last landmark of synthetic biology has been published this month in Science. A group of scientists has generated synthetic nucleic acids able to store and transmit information and also of evolving, are we in front of novel life forms?

In our cells the molecule in charge of storing and propagating genetic information is DNA (deoxyribonucleic acid). In other systems, like a huge number of viruses, these functions are performed by RNA (ribonucleic acid). Both molecules have chains formed by nucleotides, which are composed of a sugar (deoxyribose in the case of DNA and ribose for RNA), a phosphate group as a linker and a nucleobase that names each nucleotide, A, C, G or T (U instead of T in the case of RNA). Nucleobases are the letters of the genetic alphabet and the different combinations are responsible for biological diversity. Besides, A bonds only to T or U and C only hybridizes to G and the cell uses this property to translate and copy the genetic information.

The six XNA designed (image from Science)

Now an international team of scientists, led by Philipp Holliger and Vitor Pinheiro from MRC, have generated molecules very similar to DNA but built using different sugars: XNA (xeno-nucleic acids, where X represents the different sugars employed). They have produced six different molecules, using not only pentoses (5 carbon sugars as the ones used in the natural nucleic acids) but also sugars of 3, 4 and six carbons. All the XNA generated hybridize to DNA and RNA. Even if biochemically they behave  as normal nucleic acids, XNA are not recognized by natural enzymes and to multiply them Pinheiro and colleagues have designed new polymerases able to synthesize XNAs from a DNA template and others capable of producing DNA from XNA, almost without making any mistake in the replicate. As if that were not enough, one of the XNAs was evolved in the lab to bind specifically and strongly to certain target molecules, that is, to work as an aptamer, being able to affect the cellular function of the target.  In addition, as XNAs are not recognized by the cellular machinery, they cannot be degraded either, giving way to their use as therapeutic agents or biomaterials.

The study published last week in Science opens the concept of biology, exploring alternative life forms, reflecting on the most primitive life molecule and laying the foundations to create new genetic systems, independent of DNA or RNA. The task is not trivial and the next step seems to be the generation of enzymes able to synthesize XNA from XNA, without the intermediary DNA used in this study. Are these breakthroughs dangerous? When asking this question to the expert Gerald Joyce he undoubtedly answers they are not, but he warns that we have to be careful when entering areas that “have the potential to harm our biology”. There is still a lot to do, we will follow their progresses!