Genetics researchers have successfully synthesized XNA, a nucleic acid not naturally found in nature.Source: Wikipedia

Genetics researchers have successfully synthesized XNA, a nucleic acid not naturally found in nature.
Source: Wikipedia

RNA and DNA have long been established as the storage containers of genetic information in biology. However, researchers are now wondering whether RNA and DNA are inherently superior molecules for genetic storage and whether we can synthesize a new molecule to do the same job. Both questions are being answered through research in xeno-nucleic acids, or XNAs, which are nucleic acid structures not found in nature (1).

Several XNAs have already been synthesized, in which the sugar backbone of RNA or DNA (ribose or deoxyribose, respectively) is replaced with another sugar structure. The name of the backbone is then reflected in the name of the nucleic acid, e.g. the molecules with a hexose backbone are called hexitol nucleic acid, or HNA (2).

Most XNAs still use the same bases found in DNA: adenine (A), thymine (T), guanine (G), and cytosine (C). The pairing is also the same: A-T and G-C. A few of these XNAs, such as HNA, glycol nucleic acid (GNA), and threose nucleic acid (TNA), even form the same double helix structure familiar to DNA (2). If XNA were dropped into a living organism today, nothing would happen because natural polymerases cannot recognize the structure, and thus cannot decode the information stored within the base-pair sequence (2).

However, last year, scientists led by Vitor Pinheiro created several synthetic enzymes that worked with XNAs that allow them to function similar to a natural genetic storage molecule. They engineered XNA-compatible polymerases, which could create a strand of XNA using a DNA template. The most successful polymerase was able to make an HNA chain long enough to encode meaningful information, like the gene for tRNA synthesis. The group also successfully engineered reverse transcriptases (RTs), which do the opposite of an XNA polymerase — that is, make a strand of DNA from an XNA template (1). Thus, the information encoded in DNA can now be converted to an XNA and vice versa.

Pinheiro et al. showed XNAs can undergo Darwinian evolution as well. To do this, the team performed a procedure that simulated natural selection that selected for XNAs with high affinity to another molecule. After 8 rounds of the selection process, the resultant XNAs showed very strong, highly specific bonding to the target molecule (1).

First, these findings demonstrate replication and evolution are not specific to RNA and DNA (1). The fact that all life today operates using these two molecules is likely due to chance, not because they had particularly special characteristics.

Additionally, these findings all point to the possibility of a future synthetic life form based purely on XNAs (2). There are several issues concerning such a project, however. First, a whole arsenal of other enzymes must be made, including helicases, ligases, and histones, all of which must be tailored to a particular XNA. Second, an XNA organism can potentially harm an RNA/DNA organism (such as humans) if XNAs could somehow get into our own genetic information, so greater security measures must take place (2). Done right, an XNA system has the potential to be the ultimate biosafety tool. It could perhaps synthesize an important chemical or store genetic information for a molecular machine, all without affecting the DNA of a natural organism (2). Biotechnology and medicine both could benefit from these attributes (1). With XNAs, researchers ultimately hope to deepen their understanding of life and its processes, regardless of the chemical building blocks seen naturally on Earth.


1. V. B. Pinheiro et al., Science 336, 341 (2012).

2. M. Schmidt, BioEssays 32, 322 (2010).