Xeno nucleic acid
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.
5 See also
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
polymerase 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
DNA and 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 even contains a fluorine atom.[citation
needed] These substitutions make XNAs functionally and structurally
DNA and RNA, but they also make them unnatural and
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
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
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
One 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
RNA in 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 like
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
DNA and RNA's role in
life emerged through natural selection processes or if it was simply a
Nucleic acid analogue
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Types of nucleic acids
precursor, heterogenous nuclear
Small Cajal Body RNAs
Trans-acting small interfering