XDNA

{{Short description|Benzo-homologated DNA analogue}} {{About|a benzo-homologated DNA analogue|multiple video card technology by [[Diamond Multimedia]]|xDNA (multi-graphics)|AI accelerator architecture from AMD|AMD XDNA|other alternative nucleic acid coding systems|nucleic acid analogues}}{{lowercase}} {| class="wikitable floatright" |[[File:Expanded adenine.png|center|frameless]] |- !Benzo-homologated Adenine |- |[[File:Expanded thymine.png|center|frameless]] |- !Benzo-homologated Thymine |- |[[File:Expanded cytosine.png|center|frameless]] |- !Benzo-homologated Cytosine |- |[[File:Expanded guanine.png|center|frameless]] |- !Benzo-homologated Guanine |}

'''xDNA''' (also known as '''expanded DNA''' or '''benzo-homologated DNA''') is a size-expanded [[nucleotide]] system synthesized from the fusion of a [[Benzene|benzene ring]] and one of the four natural bases: [[adenine]], [[guanine]], [[cytosine]], and [[thymine]].<ref name=":7">{{cite journal | vauthors = Lynch SR, Liu H, Gao J, Kool ET | title = Toward a designed, functioning genetic system with expanded-size base pairs: solution structure of the eight-base xDNA double helix | journal = Journal of the American Chemical Society | volume = 128 | issue = 45 | pages = 14704–11 | date = November 2006 | pmid = 17090058 | pmc = 2519095 | doi = 10.1021/ja065606n | bibcode = 2006JAChS.12814704L }}</ref> This size expansion produces an 8 letter alphabet which has a larger [[Units of information#Primary_units|information storage capacity]] than natural [[DNA|DNA's]] (often referred to as B-DNA in literature) 4 letter alphabet.<ref name=":0">{{cite journal | vauthors = Gao J, Liu H, Kool ET | title = Assembly of the complete eight-base artificial genetic helix, xDNA, and its interaction with the natural genetic system | journal = Angewandte Chemie | volume = 44 | issue = 20 | pages = 3118–22 | date = May 2005 | pmid = 15834852 | doi = 10.1002/anie.200500069 | bibcode = 2005ACIE...44.3118G }}</ref> As with normal [[Base pair|base-pairing]], A pairs with xT, C pairs with xG, G pairs with xC, and T pairs with xA. The [[Nucleic acid double helix|double helix]] is thus 2.4[[Ångström|Å]] wider than a natural double helix.<ref name=":3">{{cite journal | vauthors = Fuentes-Cabrera M, Zhao X, Kent PR, Sumpter BG | title = Electronic structure of xDNA | journal = The Journal of Physical Chemistry B | volume = 111 | issue = 30 | pages = 9057–61 | date = August 2007 | pmid = 17650925 | doi = 10.1021/jp0729056 | bibcode = 2007JPCB..111.9057F }}</ref><ref name=":4">{{cite journal | vauthors = Krueger AT, Lu H, Højland T, Liu H, Gao J, Kool ET | title = Towards the replication of xDNA, a size-expanded unnatural genetic system | journal = Nucleic Acids Symposium Series | volume = 52 | issue = 1 | pages = 455–6 | date = 2008-09-01 | pmid = 18776450 | doi = 10.1093/nass/nrn231 | doi-access = free }}</ref> While similar in structure to B-DNA, xDNA has unique absorption, fluorescence, and stacking properties.<ref name=":1" /><ref name=":10" /><ref name=":2" />

Initially synthesized as an [[enzyme]] probe by Nelson J. Leonard's group, benzo-homologated adenine was the first base synthesized. Later, [[Eric Kool|Eric T. Kool]]'s group finished synthesizing the remaining three expanded [[Nitrogenous base|bases]], eventually followed by yDNA ("wide" DNA), another benzo-homologated nucleotide system, and [[Naphthalene|naphtho]]-homologated xxDNA and yyDNA. xDNA is more stable when compared to regular DNA when subjected to higher temperature, and while entire strands of xDNA, yDNA, xxDNA and yyDNA exist, they are currently difficult to synthesize and maintain. Experiments with xDNA provide new insight into the behavior of natural B-DNA. The extended bases xA, xC, xG, and xT are naturally [[fluorescence|fluorescent]], and single strands composed of only extended bases can recognize and bind to single strands of natural DNA, making them useful tools for studying biological systems.<ref name=":3" /><ref name=":5" /> xDNA is most commonly formed with base pairs between a natural and expanded [[nucleobase]], however x-nucleobases can also be paired together.<ref name=":1">{{cite journal | vauthors = McConnell TL, Wetmore SD | title = How do size-expanded DNA nucleobases enhance duplex stability? Computational analysis of the hydrogen-bonding and stacking ability of xDNA bases | journal = The Journal of Physical Chemistry B | volume = 111 | issue = 11 | pages = 2999–3009 | date = March 2007 | pmid = 17388411 | doi = 10.1021/jp0670079 | bibcode = 2007JPCB..111.2999M }}</ref> Current research supports xDNA as a viable genetic encoding system in the near future.<ref name=":4" />

== Origins == The first [[nucleotide]] to be expanded was the [[purine]] [[adenine]]. Nelson J. Leonard and colleagues synthesized this original x-nucleotide, which was referred to as "expanded adenine". xA was used as a probe in the investigation of [[active site]]s of [[Adenosine triphosphate|ATP]]-dependent [[enzyme]]s, more specifically what modifications the [[Substrate (chemistry)|substrate]] could take while still being functional.<ref name=":5" /><ref name=":6">{{cite journal | vauthors = Sharma P, Lait LA, Wetmore SD | title = Exploring the limits of nucleobase expansion: computational design of naphthohomologated (xx-) purines and comparison to the natural and xDNA purines | journal = Physical Chemistry Chemical Physics | volume = 15 | issue = 37 | pages = 15538–49 | date = October 2013 | pmid = 23942832 | doi = 10.1039/c3cp52656a | bibcode = 2013PCCP...1515538S }}</ref> Almost two decades later, the other three bases were successfully expanded and later integrated into a [[Nucleic acid double helix|double helix]] by [[Eric Kool|Eric T. Kool]] and colleagues. Their goal was to create a synthetic genetic system which mimics and surpasses the functions of the natural genetic system,<ref name=":9">{{cite journal | vauthors = Krueger AT, Lu H, Lee AH, Kool ET | title = Synthesis and properties of size-expanded DNAs: toward designed, functional genetic systems | journal = Accounts of Chemical Research | volume = 40 | issue = 2 | pages = 141–50 | date = February 2007 | pmid = 17309194 | doi = 10.1021/ar068200o | pmc=2539066}}</ref> and to broaden the applications of [[DNA]] both in living cells and in experimental [[biochemistry]]. Once the expanded base set was created, the goal shifted to identifying or developing faithful replication enzymes and further optimizing the expanded DNA alphabet.<ref name=":5">{{cite journal | vauthors = Lait LA, Rutledge LR, Millen AL, Wetmore SD | title = yDNA versus xDNA pyrimidine nucleobases: computational evidence for dependence of duplex stability on spacer location | journal = The Journal of Physical Chemistry B | volume = 112 | issue = 39 | pages = 12526–36 | date = October 2008 | pmid = 18771305 | doi = 10.1021/jp805547p | bibcode = 2008JPCB..11212526L }}</ref>

=== Synthesis === In benzo-homologated purines (xA and xG), the [[Benzene|benzene ring]] is bound to the [[nitrogenous base]] through nitrogen-carbon (N-C) bonds. Benzo-homologated pyrimidines are formed through carbon-carbon (C-C) bonds between the base and the benzene.<ref name=":3" /> Thus far, x-nucleobases have been added to strands of DNA using [[phosphoramidite]] derivatives, as traditional [[DNA polymerase|polymerases]] have been unsuccessful in synthesizing strands of xDNA. X-nucleotides are poor candidates as substrates for B-DNA polymerases as their size interferes with binding at the [[Active site|catalytic domain]]. Attempts at using [[Template strand|template-independent]] enzymes have been successful as they have a reduced geometric constraint for substrates. [[Terminal deoxynucleotidyl transferase]] (TdT) has been used previously to synthesize strands of bases which have been bound to [[fluorophore]]s. Using [[Terminal deoxynucleotidyl transferase|TdT]], up to 30 [[monomer]]s can be combined to form a double-helix of xDNA, however this [[oligomer]]ic xDNA appears to inhibit its own extension beyond this length due to the overwhelming hydrogen bonding. In order to minimize inhibition, xDNA can be hybridized into a regular helix.<ref name=":2">{{cite journal | vauthors = Jarchow-Choy SK, Krueger AT, Liu H, Gao J, Kool ET | title = Fluorescent xDNA nucleotides as efficient substrates for a template-independent polymerase | journal = Nucleic Acids Research | volume = 39 | issue = 4 | pages = 1586–94 | date = March 2011 | pmid = 20947563 | doi = 10.1093/nar/gkq853 | pmc=3045586}}</ref><ref name=":8">{{cite journal | vauthors = Heckel A | title = A new DNA analogue with expanded size and scope | journal = ChemBioChem | volume = 5 | issue = 6 | pages = 765–7 | date = June 2004 | pmid = 15174157 | doi = 10.1002/cbic.200400001 | s2cid = 26157871 }}</ref>

=== Replication === For xDNA to be used as a substitute structure for information storage, it requires a reliable replication mechanism. Research into xDNA replication using a [[Klenow fragment]] from [[DNA polymerase I]] shows that a natural base partner is selectively added in instances of single-nucleotide insertion. However, [[DNA polymerase IV]] (Dpo4) has been able to successfully use xDNA for these types of insertions with high fidelity, making it a promising candidate for future research in extending replicates of xDNA.<ref name=":4" /> xDNA's mismatch sensitivity is similar to that of [[DNA|B-DNA]].<ref name=":0" />

== Structure == {| class="wikitable floatright" border="1" cellpadding="2" cellspacing="0" align="none" style="margin-left:1em" |- align="center" | [[File:Adenin.svg|55px|Chemical structure of dxA]] | [[File:Thymine skeletal.svg|65px|Chemical structure of dxT]] | [[File:Cytosin.svg|50px|Chemical structure of dxC]] | [[File:Guanine.svg|80px|Chemical structure of dxG]] |- align="center" | [[Adenine]] | [[Thymine]] | [[Cytosine]] | [[Guanine]] |- align="center" | [[File:modified nucleobase dxA.svg|85px]] | [[File:modified nucleobase dxT.svg|85px]] | [[File:modified nucleobase dxC.svg|75px]] | [[File:modified nucleobase dxG.svg|110px]] |- align="center" | Size-expanded xA | Size-expanded xT | Size-expanded xC | Size-expanded xG |} Similar to natural bases, x-nucleotides selectively assemble into a duplex-structure resembling B-DNA.<ref name=":4" /> xDNA was originally synthesized by incorporating a benzene ring into the nitrogenous base. However, other expanded bases have been able to incorporate [[thiophene]] and [[Benzothiophene|benzo[b]thiophene]] as well. xDNA and yDNA use benzene rings to widen the bases and are thus termed "benzo-homologated". Another form of expanded nucleobases known as yyDNA incorporate [[naphthalene]] into the base and are "naptho-homologated". xDNA has a rise of 3.2[[Ångström|Å]] and a twist of 32°, significantly smaller than B-DNA, which has a rise of 3.3[[Ångström|Å]] and a twist of 34.2°<ref name=":3" /> xDNA nucleotides can occur on both strands—either alone (known as "doubly expanded DNA"<ref name=":5" />) or mixed with natural bases—or exclusively on one strand or the other. Similar to B-DNA, xDNA can recognize and bind complementary single-stranded [[DNA]] or [[RNA]] sequences.<ref name=":0" />

Duplexes formed from xDNA are similar to [[Base pair|natural duplexes]] aside from the distance between the two sugar-phosphate backbones. xDNA helices have a greater number of base pairs per turn of the helix as a result of a reduced distance between neighbour nucleotides. NMR spectra report that xDNA helices are anti-parallel, [[Chirality (chemistry)|right-handed]] and take an [[Alkane stereochemistry|''anti'' conformation]] around the [[glycosidic bond]], with a C2'-endo sugar pucker.<ref name=":1" /><ref name=":8" /> Helices created from xDNA are more likely to take a B-helix over an A-helix conformation,<ref name=":0" /> and have an increased major groove width by 6.5[[Ångström|Å]] (where the backbones are farthest apart) and decreased minor groove width by 5.5[[Ångström|Å]] (where the backbones are closest together) compared to [[DNA|B-DNA]]. Altering groove width affects the xDNA's ability to associate with [[DNA-binding protein]]s,<ref>{{cite journal | vauthors = Varghese MK, Thomas R, Unnikrishnan NV, Sudarsanakumar C | title = Molecular dynamics simulations of xDNA | journal = Biopolymers | volume = 91 | issue = 5 | pages = 351–60 | date = May 2009 | pmid = 19137576 | doi = 10.1002/bip.21137 | s2cid = 38901164 }}</ref> but as long as the expanded [[nucleotide]]s are exclusive to one strand, recognition sites are sufficiently similar to [[DNA|B-DNA]] to allow bonding of [[transcription factor]]s and small [[polyamide]] molecules. Mixed helices present the possibility of recognizing the four expanded bases using other DNA-binding molecules.<ref name=":8" />

== Properties == Expanded nucleotides and their oligomeric helices share many properties with their natural [[DNA|B-DNA]] counterparts, including their pairing preference: [[Adenine|A]] with [[Thymine|T]], [[Cytosine|C]] with [[Guanine|G]].<ref name=":8" /> The various differences in chemical properties between xDNA and [[DNA|B-DNA]] support the hypothesis that the [[Benzene|benzene ring]] which expands x-nucleobases is not, in fact, chemically inert.<ref name=":1" /> xDNA is more [[Hydrophobe|hydrophobic]] than [[DNA|B-DNA]],<ref name=":2" /> and also has a smaller [[HOMO–LUMO gap]] (distance between the highest occupied molecular orbital and lowest unoccupied molecular orbital) as a result of modified [[Saturated and unsaturated compounds|saturation]].<ref name=":3" /> xDNA has higher melting temperatures than [[DNA|B-DNA]] (a mixed decamer of xA and T has a melting temperature of 55.6&nbsp;°C, 34.3&nbsp;°C higher than the same decamer of A and T<ref name=":8" />), and exhibits an "all-or-nothing" melting behaviour.<ref name=":0" />

=== Conformation === Under lab conditions, xDNA orients itself in the [[Alkane stereochemistry|''syn'' conformation]]. This unfortunately does not expose the binding face of the xDNA nucleotides to face the neighbouring strand for binding, meaning that extra measures must be applied to alter the conformation of xDNA before attempting to form helices. However, the ''anti'' and ''syn'' orientations are practically identical energetically in expanded bases.<ref name=":6" /> This conformational preference is seen primarily in [[pyrimidine]]s, and [[purine]]s display minimal preference for orientation.<ref name=":1" />

=== Enhanced stacking === Stacking of the [[nucleotide]]s in a [[Nucleic acid double helix|double helix]] is a major determinant of the helix's stability. With the added [[surface area]] and [[hydrogen]] available for bonding, stacking potential for the nucleobases increases with the addition of a [[benzene]] spacer. By increasing the separation between the [[nitrogenous base]]s and either sugar-phosphate backbone, the helix's stacking energy is less variable and therefore more stable. The energies for natural nucleobase pairs vary from 18 to 52 kJ/mol. This variance is only 14–40 kJ/mol for xDNA.<ref name=":5" />

Due to an increased overlap between and expanded strand of [[DNA]] and its neighbouring strand, there are greater interstrand interactions in expanded and mixed helices, resulting in a significant increase in the helix's stability. xDNA has enhanced stacking abilities resultant from changes in inter- and intrastrand [[hydrogen bond]]ing that arise from the addition of a [[benzene]] spacer, but expanding the bases does not alter hydrogen's contribution to the stability of the duplex. These stacking abilities are exploited by helices consisting of both xDNA and [[DNA|B-DNA]] in order to optimize the strength of the helix. Increased stacking is seen most prominently in strands consisting only of [[Adenine|A]] and xA and [[Thymine|T]] and xT, as [[Thymine|T]]-xA has stronger stacking interactions than [[Thymine|T]]-[[Adenine|A]].<ref name=":3" />

The energy resultant from [[pyrimidine]]s ranges from 30 to 49 kJ/mol. The range for [[purine]]s is between 40-58kJ/mol. By replacing one nucleotide in a double-helix with an expanded nucleotide, the strength of the stacking interactions increases by 50%. Expanding both nucleotides results in a 90% increase in stacking strength. While xG has an overall negative effect on the binding strength of the helix, the other three expanded bases outweigh this with their positive effects. The change in energy caused by expanding the bases is mostly dependent on the [[Alkane stereochemistry|rotation of the bond]] about the nucleobases' [[Center of mass|centers of mass]], and center of mass stacking interactions improve the stacking potential of the helix.<ref name=":1" /> Because the size-expanded bases widen the helix, it is more thermally stable with a higher melting temperature.<ref name=":2" />

=== Absorption === The addition of a [[benzene]] spacer in x-[[nucleobase]]s affects the bases' [[Absorption (electromagnetic radiation)|optical absorption]] spectra. [[Time-dependent density functional theory]] (TDDFT) applied to xDNA revealed that the benzene component of the highest occupied molecular orbitals ([[HOMO/LUMO|HOMO]]) in the x-bases pins the absorption onset at an earlier point than natural [[Nitrogenous base|bases]]. Another unusual feature of xDNA absorption spectra is the red-shifted [[excimer]]s of xA in the low range. In terms of stacking fingerprints, there is a more pronounced hypochromicity seen in consecutive xA-[[Thymine|T]] [[base pair]]s.

Implications of xDNA's altered absorption include applications in [[Nanoelectronics|nanoelectronic technology]] and [[nanobiotechnology]]. The reduced spacing between x-nucleotides makes the [[Nucleic acid double helix|helix]] stiffer, thus it is not as easily affected by [[Substrate (chemistry)|substrate]], [[electrode]], and functional [[nanoparticle]] forces. Other alterations to natural [[nucleotide]]s resulting in different absorption spectra will broaden these applications in the future.<ref name=":10">{{cite journal | vauthors = Varsano D, Garbesi A, Di Felice R | title = Ab initio optical absorption spectra of size-expanded xDNA base assemblies | journal = The Journal of Physical Chemistry B | volume = 111 | issue = 50 | pages = 14012–21 | date = December 2007 | pmid = 18034470 | doi = 10.1021/jp075711z | bibcode = 2007JPCB..11114012V }}</ref>

=== Fluorescence === One unique property of xDNA is its inherent [[fluorescence]]. Natural bases can be bound directly to [[fluorophore]]s for use in [[Microarray analysis techniques|microarrays]], [[In situ hybridization|''in situ'' hybridization]], and [[Polymorphism (biology)|polymorphism]] analysis. However, these fluorescent natural bases often fail as a result of [[Quenching (fluorescence)|self-quenching]], which diminishes their fluorescent intensity and reduces their applicability as visual DNA tags. The [[pi interaction]]s between the rings in x-nucleobases result in an inherent [[fluorescence]] in the violet-blue range, with a [[Stokes shift]] between 50 and 80&nbsp;nm. They also have a [[quantum yield]] in the range of 0.3–0.6. xC has the greatest fluorescent emission.<ref name=":9" /><ref name=":2" />

== Other expanded bases == After the creation of and successful research surrounding xDNA, more forms of expanded nucleotides were investigated. yDNA is a second, similar system of nucleotides which uses a [[Benzene|benzene ring]] to expand the four [[Nucleobase|natural bases]]. xxDNA and yyDNA use [[naphthalene]], a polycyclic [[molecule]] consisting of two [[hydrocarbon]] rings. The two rings expand the base even wider, further altering its chemical properties.

=== yDNA === [[File:A bonded to xT.png|alt=Adenine forms two hydrogen bonds with expanded thymine.|thumb|296x296px|Adenine (left) bonded to x-thymine (right).]] The success and implications of xDNA prompted research to examine other factors which could alter [[Nucleic acid double helix|B-DNA]]'s chemical properties and create a new system for information storage with broader applications. yDNA also uses a [[Benzene|benzene ring]], similar to xDNA, with the only difference being the site of addition of the [[Aromaticity|aromatic ring]]. The location of the [[Benzene|benzene ring]] changes the preferred structure of the expanded helix. The altered conformation makes yDNA more similar to [[DNA|B-DNA]] in its orientation by changing the interstrand [[hydrogen bond]]s. Stability is highly dependent on the bases' rotation about the link between the base and the sugar of the backbone. yDNA's altered preference for this orientation makes it more stable overall than xDNA. The location of the [[benzene]] spacer also affects the bases' groove geometry, altering neighbour interactions. The base pairs between y-nucleotides and natural nucleotides is planar, rather than slightly twisted as with xDNA. This decreases the rise of the [[Nucleic acid double helix|helix]] even further than achieved by xDNA. [[File:A and yT.png|alt=Adenine forms two hydrogen bonds with y-thymine.|thumb|296x296px|Adenine (left) bonded to y-thymine (right).]] While xDNA and yDNA are quite similar in most properties, including their increased stacking interactions, yDNA shows superior mismatch recognition. y-pyrimidines display slightly stronger stacking interactions than x-pyrimidines as a result of the distance between the two [[anomer]]ic carbons, which is slightly larger in yDNA. xDNA still has stronger stacking interactions in model helices, but adding either x- or y-pyrimidines to a natural [[Nucleic acid double helix|double helix]] strengthens the intra- and interstrand interactions, increasing overall helix stability. In the end, which of the two has the strongest overall stacking interactions is dependent on the [[Nucleic acid sequence|sequence]]; xT and yT bind [[Adenine|A]] with similar strength, but the stacking energy of yC bound to [[Guanine|G]] is stronger than xC by 4kJ/mol. yDNA and other expanded bases are part of a very young field which is highly understudied. Research suggest that the ideal conformation still remains to be discovered, but knowing that the [[benzene]] location affects the orientation and structure of expanded nucleobases adds information to their future design.<ref name=":5" />

=== yyDNA and xxDNA === [[File:XxA ball and stick.png|alt=Naphthohomologated Adenine (xxA) incorporates the two-ringed naphthalene structure between its two native rings.|thumb|207x207px|Naphtho-homologated Adenine (xxA)|left]] Doubly-expanded (or ''naphtho-homologated'') nucleobases incorporate a [[naphthalene]] spacer instead of a [[Benzene|benzene ring]], widening the base twice as much with its two-ringed structure. These structures (known as xxDNA and yyDNA) are 4.8[[Ångström|Å]] wider than [[Nucleobase|natural bases]] and were once again created as a result of Leonard's research on expanded [[adenine]] in [[Adenosine triphosphate|ATP]]-dependent [[enzyme]]s in 1984. No literature was published on these doubly-expanded bases for nearly three decades until 2013 when the first xxG was produced by Sharma, Lait, and Wetmore and incorporated along with xxA into a [[Nucleic acid double helix|natural helix]]. Although very little research has been performed on xxDNA, xx-[[purine]] neighbours have already been shown to increase intrastrand stacking energy by up to 119% (as opposed to 62% in x-purines). xx-[[purine]] and [[pyrimidine]] interactions show an overall decrease in stacking energies, but the overall stability of [[Base pair|duplexes]] including pyrimidines and xx-purines increases by 22%, more than twofold that of pyrimidines and x-purines.<ref name=":6" />

== Uses == xDNA has many applications in chemical and biological research, including expanding upon applications of natural [[DNA]], such as scaffolding. In order to create self-assembling nanostructures, a scaffold is needed as a sort of [[Trellis (architecture)|trellis]] to support the growth. DNA has been used as a means to this end in the past, but expanded scaffolds make larger scaffolds for more complex self-assembly an option.<ref name=":7" /> xDNA's [[Electrical resistivity and conductivity|electrical conduction]] properties also make it a prime candidate as a [[molecular wire]], as its [[Pi interaction|π-π interactions]] help it efficiently conduct electricity.<ref name=":3" /> Its 8-letter alphabet ([[Adenine|A]], [[Thymine|T]], [[Cytosine|C]], [[Guanine|G]], xA, xT, xC, xG) gives it the potential to store 2ⁿ times more states per [[Nucleic acid sequence|sequence]] than DNA, where ''n'' is the number of bases in the sequence. For example, combining 6 nucleotides of with [[DNA|B-DNA]] yields 4096 possible sequences, whereas a combination of the same number of nucleotides created with xDNA yields 262,144 possible sequences. Additionally, xDNA can be used as a fluorescent probe at enzyme [[active site]]s, as was its original application by Leonard et al.<ref name=":0" />

xDNA has also been applied to the study of [[Protein–DNA interaction|protein-DNA interactions]]. Due to xDNA's natural [[Fluorescence|fluorescing]] properties, it can easily be visualized in both lab and living conditions.<ref name=":1" /> xDNA is becoming more easy to create and [[oligomer]]ize, and its high-affinity binding to [[Complementary DNA|complementary]] [[DNA]] and [[RNA]] sequences means that it can not only help locate these sequences floating around in the cell, but also when they are already interacting with other structures within the cell.<ref name=":9" /> xDNA also has potential applications in assays that employ [[Terminal deoxynucleotidyl transferase|TdT]] as it may improve reporters, and can be used as an [[Chemical affinity|affinity tag]] for interstrand bonding.<ref name=":2" />

== See also == * [[DNA]] * [[RNA]] * [[DNA sequencing]] * [[Genetic engineering]] * [[Nanobiotechnology]] * [[Nucleobase]] * [[Hachimoji DNA]] * [[Artificially Expanded Genetic Information System]] (AEGIS)

== References == {{Reflist}}

[[Category:Biochemistry methods]] [[Category:DNA]] [[Category:Genetics techniques]] [[Category:Molecular biology]]