XENO NUCLEIC ACID (XNA) is a synthetic alternative to the natural
RNA as information-storing biopolymers that
differs in the sugar backbone. As of 2011, 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 .
Although the genetic information is still stored in the four
canonical base pairs (unlike other nucleic acid analogues ), natural
DNA polymerases cannot read and duplicate this information. Thus the
genetic information stored in XNA is “invisible” and therefore
useless to natural DNA-based organisms.
* 1 Background
* 2 Structure
* 3 Implications
* 4 Applications
* 5 See also
* 6 References
The structure of the
DNA was discovered in 1953 and many scientists
assumed that our understandings for the chemical basis of life was
perfect. However, around the early 2000s, researchers were able to
create 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, named by scientists to indicate the
difference in the molecular structure of XNA when compared to
RNA. Not much was done with XNA until the development of special
Enzyme , capable of copying XNA from a
DNA template as well
as copying XNA back into DNA. More recently, synthetic biologists
Philipp Holliger and Alexander Taylor, both from the University of
Cambridge, managed to create XNAzymes, the XNA equivalent of a
Ribozyme , enzymes made of
DNA or ribonucleic acid; 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.
This image displays the differences in the sugar backbones used
in XNAs compared to common and biologically used
DNA and RNA.
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
RNA , with one exception: in
XNA nucleotides , the deoxyribose and ribose sugar groups of
RNA have been replaced. Some of these replacement molecules contain
four carbons atoms instead of the standard five. Others cram in as
many as seven carbons. FANA (pictured top right) even contains a
fluorine atom. These substitutions make XNAs functionally and
structurally analogous to
RNA , but they also make them
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) and cyclohexene nucleic acid
Threose nucleic acid (TNA ), glycol nucleic acid (GNA ),
locked nucleic acid (LNA ), and peptide nucleic acid (PNA ) are also
other currently known XNAs that have been made and have more
background information currently available than the previous two
mentioned. 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.
The study of XNA is intended not 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
DNA nucleotide bases yields endless opportunities
for genetic modification and expansion of chemical functionality.
The development of various hypotheses and theories about XNAs have
altered a key factor in our current understanding of nucleic acids:
that heredity and evolution are not limited to
RNA as once
thought, but are simply processes that have developed from polymers
capable of storing information. Investigations into XNAs will allow
for researchers to assess whether
RNA are the most efficient
and desirable building blocks of life, or if these two molecules were
chosen randomly after evolving from a larger class of chemical
What makes XNA potentially more desirable than
RNA in genetic
research is that it can easily adapt to in vitro environments and can
even pass genetic information across generations when constrained in a
test tube. Another theory of XNA utilization is its incorporation into
medicine as a disease-fighting agent. Some enzymes and antibodies that
are currently administered for various disease treatments are broken
down too quickly in the stomach or bloodstream. Because XNA is foreign
and because it is believed that humans have not yet evolved the
enzymes to break them down, XNAs may be able to serve as a more
durable counterpart to the
DNA and RNA-based treatment methodologies
that are currently in use.
Experiments with XNA have already allowed for the replacement and
enlargement of this genetic alphabet, and XNAs have shown
RNA nucleotides, suggesting potential for
its transcription and recombination. One experiment conducted at the
University of Florida led to the production of an XNA aptamer by the
AEGIS-SELEX (artificially expanded genetic information system -
systematic evolution of ligands by exponential enrichment) method,
followed by successful binding to a line of breast cancer cells.
Furthermore, experiments in the model bacterium E. coli have
demonstrated the ability for XNA to serve as a biological template for
DNA in vivo .
In moving forward with genetic research on XNAs, various questions
must come into consideration regarding biosafety , biosecurity ,
ethics, and governance/regulation. One of the key questions here is
whether XNA in an in vivo setting would intermix with
its natural environment, thereby rendering scientists unable to
control or predict its implications in genetic mutation .
XNA also has potential applications to be used as catalysts , much
RNA has the ability to be used as an enzyme . Researchers have
shown XNA is able to cleave and ligate DNA,
RNA and other XNA
sequences, with the most activity being XNA catalyzed reactions on XNA
molecules. This research may be used in determining whether
RNA's role in life emerged through natural selection processes or if
it was simply a coincidental occurrence.
Nucleic acid analogue
* ^ Markus Schmidt (9 May 2012). Synthetic Biology. John Wiley &
Sons. pp. 151–. ISBN 978-3-527-65926-5 . Retrieved 9 May 2013.
* ^ A B C Schmidt, Markus (April 2010). "Xenobiology: A new form of
life as the ultimate biosafety tool" .
John Wiley & Sons
John Wiley & Sons .
32 (4): 322–331. PMC 2909387 . PMID 20217844 . doi
* ^ Gonzales, Robbie. "XNA Is Synthetic
DNA That's Stronger than
the Real Thing." Web log post. Io9, 09 Apr. 2012. Web. 15 Oct. 2015. .
* ^ Medical Research Council "World's first artificial enzymes