Xeno nucleic acids (XNA) are synthetic nucleic acid analogues that have a different backbone than the ribose and deoxyribose found in the nucleic acids of naturally occurring RNA and DNA.
The same nucleobases can be used to store genetic information and interact with DNA, RNA, or other XNA bases, but the change of backbone makes the structure have different stability and cannot be processed by naturally occurring cellular processes. For example, natural DNA polymerases cannot read and duplicate this information, thus the genetic information stored in XNA is invisible to DNA-based organisms.
, at least six types of synthetic sugars have been shown to form nucleic acid backbones that can store and retrieve genetic information. Research is now being done to create synthetic polymerases to transform XNA. The study of its production and application has created a field known as xenobiology.
Background
The structure of DNA was discovered in 1953. Around the early 2000s, researchers created a number of exotic DNA-like structures, XNA. XNA is a synthetic polymer that can carry the same information as DNA, but with different molecular constituents. The "X" in XNA stands for "xeno," meaning stranger or alien, indicating the difference in the molecular structure as compared to DNA or RNA.
Not much was done with XNA until the development of special polymerase enzyme, capable of copying XNA from a DNA template as well as copying XNA back into DNA. Pinheiro et al. (2012), for example, has demonstrated such an XNA-capable polymerase that works on sequences of ~100bp in length. More recently, synthetic biologists Philipp Holliger and Alexander Taylor managed to create XNAzymes, the XNA equivalent of a ribozyme, enzymes made of RNA. This demonstrates that XNAs not only store hereditary information, but can also serve as enzymes, raising the possibility that life elsewhere could have begun with something other than RNA or DNA.
Structure
Strands of DNA and RNA are formed by stringing together long chains of molecules called nucleotides. A nucleotide is made up of three chemical components: a phosphate, a five-carbon sugar group (this can be either a deoxyribose sugar—which gives us the "D" in DNA—or a ribose sugar—the "R" in RNA), and one of five standard bases (adenine, guanine, cytosine, thymine or uracil).
The molecules that piece together to form the six xeno nucleic acids are almost identical to those of DNA and RNA, with one exception: in XNA nucleotides, the deoxyribose and ribose sugar groups of DNA and RNA have been replaced with other chemical structures. These substitutions make XNAs functionally and structurally analogous to DNA and RNA despite being unnatural and artificial.
XNA exhibits a variety of structural chemical changes relative to its natural counterparts. Types of synthetic XNA created so far include: 1,5-Anhydrohexitol nucleic acid (HNA) Cyclohexene nucleic acid (CeNA) Threose nucleic acid (TNA) Glycol nucleic acid (GNA) Locked nucleic acid Peptide nucleic acid (PNA) Fluoroarabino nucleic acid (FANA)
HNA could be used to potentially act as a drug that can recognize and bind to specified sequences. Scientists have been able to isolate HNAs for the possible binding of sequences that target HIV. With cyclohexene nucleic acid, research has shown that CeNAs with stereochemistry similar to the D form can create stable duplexes with itself and RNA. It was shown that CeNAs are not as stable when they form duplexes with DNA.
Implications
The study of XNA is not intended to give scientists a better understanding of biological evolution as it has occurred historically, but rather to explore ways in which we can control and even reprogram the genetic makeup of biological organisms moving forward. XNA has shown significant potential in solving the current issue of genetic pollution in genetically modified organisms. While DNA is incredibly efficient in its ability to store genetic information and lend complex biological diversity, its four-letter genetic alphabet is relatively limited. Using a genetic code of six XNAs rather than the four naturally occurring DNA nucleotide bases yields endless opportunities for genetic modification and expansion of chemical functionality.