DNA walker
{{Short description|Nucleic acid nanomachine}}
A DNA walker is a class of nucleic acid nanomachines where a nucleic acid "walker" is able to move along a nucleic acid "track". The concept of a DNA walker was first defined and named by John H. Reif in 2003.{{Cite journal |title = The Design of Autonomous DNA Nanomechanical Devices: Walking and Rolling DNA| vauthors = Reif JH |date = 2003|journal = Natural Computing|volume = 2|issue = 15|pages = 439–461|doi = 10.1023/B:NACO.0000006775.03534.92|citeseerx = 10.1.1.4.291| s2cid = 6200417 }}
A nonautonomous DNA walker requires external changes for each step, whereas an autonomous DNA walker progresses without any external changes. Various nonautonomous DNA walkers were developed, for example Shin {{cite journal | vauthors = Shin JS, Pierce NA | title = A synthetic DNA walker for molecular transport | journal = Journal of the American Chemical Society | volume = 126 | issue = 35 | pages = 10834–10835 | date = September 2004 | pmid = 15339155 | doi = 10.1021/ja047543j | url = https://resolver.caltech.edu/CaltechAUTHORS:20170224-152823096 }} controlled the motion of DNA walker by using 'control strands' which needed to be manually added in a specific order according to the template's sequence in order to get the desired path of motion.
In 2004 the first autonomous DNA walker, which did not require external changes for each step, was experimentally demonstrated by the Reif group. {{cite journal | vauthors = Yin P, Yan H, Daniell XG, Turberfield AJ, Reif JH | title = A unidirectional DNA walker that moves autonomously along a track | journal = Angewandte Chemie | volume = 43 | issue = 37 | pages = 4906–4911 | date = September 2004 | pmid = 15372637 | doi = 10.1002/anie.200460522 }}
DNA walkers have functional properties such as a range of motion extending from linear to 2 and 3-dimensional, the ability to pick up and drop off molecular cargo,{{cite journal | vauthors = Thubagere AJ, Li W, Johnson RF, Chen Z, Doroudi S, Lee YL, Izatt G, Wittman S, Srinivas N, Woods D, Winfree E, Qian L | display-authors = 6 | title = A cargo-sorting DNA robot | journal = Science | volume = 357 | issue = 6356 | pages = eaan6558 | date = September 2017 | pmid = 28912216 | doi = 10.1126/science.aan6558 | doi-access = free }} performing DNA-templated synthesis, and increased velocity of motion. DNA walkers have potential applications ranging from nanomedicine to nanorobotics.{{cite journal | vauthors = Simmel FC | title = Processive motion of bipedal DNA walkers | journal = ChemPhysChem | volume = 10 | issue = 15 | pages = 2593–2597 | date = October 2009 | pmid = 19739195 | doi = 10.1002/cphc.200900493 }}{{cite journal | vauthors = Pan J, Li F, Cha TG, Chen H, Choi JH | title = Recent progress on DNA based walkers | journal = Current Opinion in Biotechnology | volume = 34 | pages = 56–64 | date = August 2015 | pmid = 25498478 | doi = 10.1016/j.copbio.2014.11.017 }} Many different fuel options have been studied including DNA hybridization, hydrolysis of DNA or ATP, and light.{{cite journal | vauthors = You M, Chen Y, Zhang X, Liu H, Wang R, Wang K, Williams KR, Tan W | display-authors = 6 | title = An autonomous and controllable light-driven DNA walking device | journal = Angewandte Chemie | volume = 51 | issue = 10 | pages = 2457–2460 | date = March 2012 | pmid = 22298502 | pmc = 3843772 | doi = 10.1002/anie.201107733 }}{{cite journal | vauthors = Škugor M, Valero J, Murayama K, Centola M, Asanuma H, Famulok M | title = Orthogonally Photocontrolled Non-Autonomous DNA Walker | journal = Angewandte Chemie | volume = 58 | issue = 21 | pages = 6948–6951 | date = May 2019 | pmid = 30897257 | doi = 10.1002/anie.201901272 | s2cid = 85446523 }} The DNA walker's function is similar to that of the proteins dynein and kinesin.
Role in DNA nanotechnology
Finding a suitable nanoscale motor capable of autonomous, unidirectional, linear motion is considered important to the development of DNA nanotechnology. The walkers have been shown to be capable of autonomous motion over linear, 2-dimensional and 3-dimensional DNA 'tracks' through a large number of schemes. In July 2005, Bath et al. showed that another way to control DNA walker motion is to use restriction enzymes to strategically cleave the 'track', causing the forward motion of the walkers.{{Cite journal|title = A free-running DNA motor powered by a nicking enzyme| vauthors = Bath J |date = July 11, 2005|journal = Angewandte Chemie International Edition|volume = 117|issue = 28|pages = 4432–4435|doi = 10.1002/ange.200501262| bibcode = 2005AngCh.117.4432B }} In 2010, two different sets of researchers exhibited the walkers' more complex abilities to selectively pick up and drop off molecular cargo{{cite journal | vauthors = Lund K, Manzo AJ, Dabby N, Michelotti N, Johnson-Buck A, Nangreave J, Taylor S, Pei R, Stojanovic MN, Walter NG, Winfree E, Yan H | display-authors = 6 | title = Molecular robots guided by prescriptive landscapes | journal = Nature | volume = 465 | issue = 7295 | pages = 206–210 | date = May 2010 | pmid = 20463735 | pmc = 2907518 | doi = 10.1038/nature09012 | bibcode = 2010Natur.465..206L }}{{cite journal | vauthors = Gu H, Chao J, Xiao SJ, Seeman NC | title = A proximity-based programmable DNA nanoscale assembly line | journal = Nature | volume = 465 | issue = 7295 | pages = 202–205 | date = May 2010 | pmid = 20463734 | pmc = 2872101 | doi = 10.1038/nature09026 | bibcode = 2010Natur.465..202G }} and to perform DNA-templated synthesis as the walker moves along the track.{{cite journal | vauthors = He Y, Liu DR | title = Autonomous multistep organic synthesis in a single isothermal solution mediated by a DNA walker | journal = Nature Nanotechnology | volume = 5 | issue = 11 | pages = 778–782 | date = November 2010 | pmid = 20935654 | pmc = 2974042 | doi = 10.1038/nnano.2010.190 | bibcode = 2010NatNa...5..778H }} In late 2015, Yehl et al. showed that three orders of magnitude higher than the speeds of motion seen previously were possible when using DNA-coated spherical particles that would "roll" on a surface modified with RNA complementary to the nanoparticle's DNA. RNase H was used to hydrolyse the RNA, releasing the bound DNA and allowing the DNA to hybridize to RNA further downstream.{{cite journal | vauthors = Yehl K, Mugler A, Vivek S, Liu Y, Zhang Y, Fan M, Weeks ER, Salaita K | display-authors = 6 | title = High-speed DNA-based rolling motors powered by RNase H | journal = Nature Nanotechnology | volume = 11 | issue = 2 | pages = 184–190 | date = February 2016 | pmid = 26619152 | pmc = 4890967 | doi = 10.1038/nnano.2015.259 | bibcode = 2016NatNa..11..184Y }} In 2018, Valero et al. described a DNA walker based on two interlocked, catenated circular double-stranded DNAs (dsDNAs) and an engineered T7 RNA polymerase (T7RNAP) firmly attached to one of the DNA circles.{{cite journal | vauthors = Valero J, Pal N, Dhakal S, Walter NG, Famulok M | title = A bio-hybrid DNA rotor-stator nanoengine that moves along predefined tracks | journal = Nature Nanotechnology | volume = 13 | issue = 6 | pages = 496–503 | date = June 2018 | pmid = 29632399 | pmc = 5994166 | doi = 10.1038/s41565-018-0109-z | bibcode = 2018NatNa..13..496V }} This stator-ring unidirectionally rotated the interlocked rotor-ring by rolling circle transcription (RCT), driven by nucleotide triphosphate (NTP) hydrolysis, thereby constituting a catenated DNA wheel motor. The wheel motor produces long, repetitive RNA transcripts that remain attached to the DNA-catenane and are used to guide its directional walking along predefined ssDNA tracks arranged on a DNA nanotube.
Applications
The applications of DNA walkers include nanomedicine,{{Cite book|title = Nanomedical Device and Systems Design: Challenges, Possibilities, Visions|url = https://books.google.com/books?id=7PHRBQAAQBAJ|publisher = CRC Press|date = Nov 18, 2013|isbn = 9781439863237| vauthors = Boehm F }} diagnostic sensing of biological samples,{{Cite web|title = Nano-walkers take speedy leap forward with first rolling DNA-based motor|url = http://phys.org/news/2015-12-nano-walkers-speedy-dna-based-motor.html|website = phys.org|access-date = 2015-12-04}} nanorobotics{{Cite web|title = Chapter 18 : DNA Nano Robotics – NanoTechnology Journal & Publications|url = http://nanotechnologypublications.com/chapter-18-dna-nano-robotics/|website = NanoTechnology Journal & Publications|access-date = 2015-12-04|language = en-US|archive-url = https://web.archive.org/web/20151208131433/http://nanotechnologypublications.com/chapter-18-dna-nano-robotics/|archive-date = 2015-12-08|url-status = dead}} and much more.{{Cite journal|title = Synthetic DNA Walkers| vauthors = Leigh D |date = April 2014|journal = Top Curr Chem|volume = 354|pages = 111–38|doi = 10.1007/128_2014_546|pmid = 24770565|series = Topics in Current Chemistry|isbn = 978-3-319-08677-4}} In late 2015, Yehl et al. improved the DNA walker's function by increasing its velocity, and it has been proposed as the basis for a low-cost, low-tech diagnostics machine capable of detecting single nucleotide mutations and heavy-metal contamination in water. In 2018 Nils Walter and his team designed a DNA walker that is capable of moving at a speed of 300 nanometres per minute. This is an order of magnitude faster than the pace of other types of DNA walker.{{cite journal | vauthors = | title = Gymnastic feats help DNA 'walker' set speed record | language = en-US | journal = Nature | volume = 557 | issue = 7705 | pages = 283 | date = May 2018 | pmid = 29760489 | doi = 10.1038/d41586-018-05127-8 | doi-access = free }}