338:
initiated by the geminiviral replication initiator protein, Rep, which is also responsible for altering the host environment to act as part of the replication machinery. Rep is also strikingly similar to most other rolling replication initiator proteins of eubacteria, with the presence of motifs I, II, and III at is N terminus. During the rolling circle replication, the ssDNA of geminivirus is converted to dsDNA and Rep is then attached to the dsDNA at the origin sequence TAATATTAC. After Rep, along with other replication proteins, binds to the dsDNA it forms a stem loop where the DNA is then cleaved at the nanomer sequence causing a displacement of the strand. This displacement allows the replication fork to progress in the 3’ to 5’ direction which ultimately yields a new ssDNA strand and a concatameric DNA strand.
330:(HPV-16) is another virus that employs rolling replication to produce progeny at a high rate. HPV-16 infects human epithelial cells and has a double stranded circular genome. During replication, at the origin, the E1 hexamer wraps around the single strand DNA and moves in the 3' to 5' direction. In normal bidirectional replication, the two replication proteins will disassociate at time of collision, but in HPV-16 it is believed that the E1 hexamer does not disassociate, hence leading to a continuous rolling replication. It is believed that this replication mechanism of HPV may have physiological implications into the integration of the virus into the host chromosome and eventual progression into cervical cancer.
380:
circular RNA. This is called the asymmetric pathway of rolling circle replication. The viroids in the family
Avsunviroidae (ASBVd-like) replicate their genome through the symmetric pathway of rolling circle replication. In this symmetric pathway, oligomeric minus strands are first cleaved and ligated to form monomeric minus strands, and then are transcribed into oligomeric plus strands. These oligomeric plus strands are then cleaved and ligated to reform the monomeric plus strand. The symmetric replication pathway was named because both plus and minus strands are produced the same way.
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HRCA, where primers that anneal to the original RCA products are added, and also extended. In this way the original RCA creates more template that can be amplified. Another is circle to circle amplification or C2CA, where the RCA products are digested with a restriction enzyme and ligated into new circular templates using a restriction oligo, followed by a new round of RCA with a larger amount of circular templates for amplification.
133:
502:
231:. Using the unnicked strand as a template, replication proceeds around the circular DNA molecule, displacing the nicked strand as single-stranded DNA. Displacement of the nicked strand is carried out by a host-encoded helicase called PcrA (the abbreviation standing for plasmid copy reduced) in the presence of the plasmid replication initiation protein.
379:
In the family
Pospiviroidae (PSTVd-like), the circular plus strand RNA is transcribed by a host RNA polymerase into oligomeric minus strands and then oligomeric plus strands. These oligomeric plus strands are cleaved by a host RNase and ligated by a host RNA ligase to reform the monomeric plus strand
337:
also utilizes rolling circle replication as its replication mechanism. It is a virus that is responsible for destroying many major crops, such as cassava, cotton, legumes, maize, tomato and okra. The virus has a circular, single stranded, DNA that replicates in host plant cells. The entire process is
580:
In addition to antibody mediated immuno-RCA, the ssDNA RCA primer can be conjugated to the 3' end of a DNA aptamer as well. The primer tail can be amplified through rolling circle amplification. The product can be visualized through the labeling of fluorescent reporter. The process is illustrated in
492:
RCA produces a linear amplification of DNA, as each circular template grows at a given speed for a certain amount of time. To increase yield and achieve exponential amplification as PCR does, several approaches have been investigated. One of them is the hyperbranched rolling circle amplification or
222:
is initiated by an initiator protein encoded by the plasmid or bacteriophage DNA, which nicks one strand of the double-stranded, circular DNA molecule at a site called the double-strand origin, or DSO. The initiator protein remains bound to the 5' phosphate end of the nicked strand, and the free 3'
509:
RCA can amplify a single molecular binding event over a thousandfold, making it particularly useful for detecting targets with ultra-low abundance. RCA reactions can be performed in not only free solution environments, but also on a solid surface like glass, micro- or nano-bead, microwell plates,
459:
for RNA amplification. Since Phi29 DNA polymerase has the best processivity and strand displacement ability among all aforementioned polymerases, it has been most frequently used in RCA reactions. Different from polymerase chain reaction (PCR), RCA can be conducted at a constant temperature (room
534:
Immuno-RCA follows a typical immuno-adsorbent reaction in ELISA or immunohistochemistry tissue staining. The detection antibodies used in immuno-RCA reaction are modified by attaching a ssDNA oligonucleotide on the end of the heavy chains. So the Fab (Fragment, antigen binding) section on the
526:
Immuno-RCA is an isothermal signal amplification method for high-specificity & high-sensitivity protein detection and quantification. This technique combines two fields: RCA, which allows nucleotide amplification, and immunoassay, which uses antibodies specific to intracellular or free
889:
Rizvi, Irum; Choudhury, Nirupam Roy; Tuteja, Narendra (2015-02-01). "Insights into the functional characteristics of geminivirus rolling-circle replication initiator protein and its interaction with host factors affecting viral DNA replication".
589:
Various derivatives of RCA were widely used in the field of biosensing. For example, RCA has been successfully used for detecting the existence of viral and bacterial DNA from clinical samples, which is very beneficial for rapid diagnostics of
415:
technique where the polymerase continuously adds single nucleotides to a primer annealed to a circular template which results in a long concatemer ssDNA that contains tens to hundreds of tandem repeats (complementary to the circular template).
1133:
Ali, M. Monsur; Li, Feng; Zhang, Zhiqing; Zhang, Kaixiang; Kang, Dong-Ku; Ankrum, James A.; Le, X. Chris; Zhao, Weian (2014-05-21). "Rolling circle amplification: a versatile tool for chemical biology, materials science and medicine".
645:
Ali, M. Monsur; Li, Feng; Zhang, Zhiqing; Zhang, Kaixiang; Kang, Dong-Ku; Ankrum, James A.; Le, X. Chris; Zhao, Weian (2014). "Rolling circle amplification: a versatile tool for chemical biology, materials science and medicine".
527:
biomarkers. As a result, immuno-RCA gives a specific amplified signal (high signal-to-noise ratio), making it suitable for detecting, quantifying and visualizing low abundance proteic markers in liquid-phase immunoassays and
473:-induced single-strand DNA elongation. Multiple primers can be employed to hybridize with the same circle. As a result, multiple amplification events can be initiated, producing multiple RCA products ("Multiprimed RCA").
359:
Some RNA viruses and viroids also replicate their genome through rolling circle RNA replication. For viroids, there are two alternative RNA replication pathways that respectively followed by members of the family
407:
from very small amounts of starting material. This amplification technique is named as rolling circle amplification (RCA). Different from conventional DNA amplification techniques such as
467:
Circular template ligation, which can be conducted via template mediated enzymatic ligation (e.g., T4 DNA ligase) or template-free ligation using special DNA ligases (i.e., CircLigase).
1505:
Zhao, Weian; Ali, M. Monsur; Brook, Michael A.; Li, Yingfu (2008-08-11). "Rolling Circle
Amplification: Applications in Nanotechnology and Biodetection with Functional Nucleic Acids".
1548:
Zhou, Long; Ou, Li-Juan; Chu, Xia; Shen, Guo-Li; Yu, Ru-Qin (2007-10-01). "Aptamer-Based
Rolling Circle Amplification: A Platform for Electrochemical Detection of Protein".
1082:
Flores, Ricardo; Gas, María-Eugenia; Molina-Serrano, Diego; Nohales, María-Ángeles; Carbonell, Alberto; Gago, Selma; De la Peña, Marcos; Daròs, José-Antonio (2009-09-14).
1356:
Zhou, Long; Ou, Li-Juan; Chu, Xia; Shen, Guo-Li; Yu, Ru-Qin (2007). "Aptamer-Based
Rolling Circle Amplification: A Platform for Electrochemical Detection of Protein".
518:). In this way, RCA is becoming a highly versatile signal amplification tool with wide-ranging applications in genomics, proteomics, diagnosis and biosensing.
1299:
Schweitzer, Barry; Roberts, Scott; Grimwade, Brian; Shao, Weiping; Wang, Minjuan; Fu, Qin; Shu, Quiping; Laroche, Isabelle; Zhou, Zhimin (April 2002).
601:
In addition to the amplification function in biosensing applications, RCA technique can be applied to the construction of DNA nanostructures and DNA
476:
Amplification product detection and visualization, which is most commonly conducted through fluorescent detection, with fluorophore-conjugated dNTP,
941:
Bernstein H, Bernstein C (July 1973). "Circular and branched circular concatenates as possible intermediates in bacteriophage T4 DNA replication".
1448:
Gusev, Y.; Sparkowski, J.; Raghunathan, A.; Ferguson, H.; Montano, J.; Bogdan, N.; Schweitzer, B.; Wiltshire, S.; Kingsmore, S. F. (July 2001).
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234:
Continued DNA synthesis can produce multiple single-stranded linear copies of the original DNA in a continuous head-to-tail series called a
1650:"Application of Hyperbranched Rolling Circle Amplification for Direct Detection of Mycobacterium Tuberculosis in Clinical Sputum Specimens"
1593:"Rolling Circle Amplification for Direct Detection of rpoB Gene Mutations in Mycobacterium tuberculosis Isolates from Clinical Specimens"
100:
53:
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Liu, Yang; Guo, Yan-Ling; Jiang, Guang-Lu; Zhou, Shi-Jie; Sun, Qi; Chen, Xi; Chang, Xiu-Jun; Xing, Ai-Ying; Du, Feng-Jiao (2013-06-04).
72:
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Chen, Xiaoyou; Wang, Bin; Yang, Wen; Kong, Fanrong; Li, Chuanyou; Sun, Zhaogang; Jelfs, Peter; Gilbert, Gwendolyn L. (2014-05-01).
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as well. The products of RCA can also be use as templates for periodic assembly of nanospecies or proteins, synthesis of metallic
79:
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3. The complementary sequence of the circular DNA template is copied hundreds of times and remains attached to the antibody.
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microfluidic devices or even paper strips. This feature makes it a very powerful tool for amplifying signals in solid-phase
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4. RCA output (elongated ssDNA) is detected with fluorescent probes using a fluorescent microscope or a microplate reader.
549:
1. A detection antibody recognizes a specific proteic target. This antibody is also attached to an oligonucleotide primer.
535:
detection antibody can still bind to specific antigens and the oligonucleotide can serve as a primer of the RCA reaction.
775:"Cloning human herpes virus 6A genome into bacterial artificial chromosomes and study of DNA replication intermediates"
68:
1177:
Lizardi, Paul M.; Huang, Xiaohua; Zhu, Zhengrong; Bray-Ward, Patricia; Thomas, David C.; Ward, David C. (July 1998).
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2. When circular DNA is present, it is annealed, and the primer matches to the circular DNA complementary sequence.
1715:
Guo, Maoxiang; Hernández-Neuta, Iván; Madaboosi, Narayanan; Nilsson, Mats; Wijngaart, Wouter van der (2018-02-12).
245:
and DNA polymerase III then replicate the single-stranded origin (SSO) DNA to make another double-stranded circle.
1450:"Rolling circle amplification: a new approach to increase sensitivity for immunohistochemistry and flow cytometry"
1232:
Dahl, Fredrik; Banér, Johan; Gullberg, Mats; Mendel-Hartvig, Maritha; Landegren, Ulf; Nilsson, Mats (2004-03-30).
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First, the initiator protein makes another nick in the DNA to terminate synthesis of the first (leading) strand.
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57:
17:
1033:
Tsagris, Efthimia Mina; Martínez de Alba, Ángel Emilio; Gozmanova, Mariyana; Kalantidis, Kriton (2008-11-01).
238:. These linear copies can be converted to double-stranded circular molecules through the following process:
594:. It has also been used as an on-chip signal amplification method for nucleic acid (for both DNA and RNA)
308:(HHV-6)(hibv) expresses a set of "early genes" that are believed to be involved in this process. The long
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temperature to 65C) in both free solution and on top of immobilized targets (solid phase amplification).
93:
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224:
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The derivative form of rolling circle replication has been successfully used for amplification of
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Björkesten, Johan; Patil, Sourabh; Fredolini, Claudia; Lönn, Peter; Landegren, Ulf (2020-05-29).
341:
46:
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replicate their genomic information in host cells via rolling circle replication. For instance,
1179:"Mutation detection and single-molecule counting using isothermal rolling-circle amplification"
312:
that result are subsequently cleaved between the pac-1 and pac-2 regions of HHV-6's genome by
834:"Rolling circle replication of human papillomavirus type 16 DNA in epithelial cell extracts"
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371:
179:. Some eukaryotic viruses also replicate their DNA or RNA via the rolling circle mechanism.
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structure present in the
Avsunviroidae, but such structure is absent in the Pospiviroidae.
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technique, rolling circle amplification was developed. The RCA mechanism is widely used in
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structures. These structures likely reflect a rolling circle mechanism of replication.
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Rolling Circle
Amplification (RCA) - Toward New Clinical | Vadim V. Demidov | Springer
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Cleavage of the oligomeric plus and minus strands is mediated by the self-cleaving
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Rolling circle replication produces multiple copies of a single circular template.
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replication that can rapidly synthesize multiple copies of circular molecules of
1393:"A multiplex platform for digital measurement of circular DNA reaction products"
726:"The molecular biology of human herpesvirus-6 latency and telomere integration"
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1301:"Multiplexed protein profiling on microarrays by rolling-circle amplification"
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Displaced DNA is a lagging strand and is made double stranded via a series of
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There are five important components required for performing a RCA reaction:
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joins the ends to make another molecule of double-stranded circular DNA.
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1234:"Circle-to-circle amplification for precise and sensitive DNA analysis"
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As a summary, a typical DNA rolling circle replication has five steps:
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Daròs, José-Antonio; Elena, Santiago F.; Flores, Ricardo (June 2006).
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Kusumoto-Matsuo, Rika; Kanda, Tadahito; Kukimoto, Iwao (2011-01-01).
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1717:"Efficient DNA-assisted synthesis of trans-membrane gold nanowires"
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The typical antibody mediated immuno-RCA procedure is as follows:
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There are typically three steps involved in a DNA RCA reaction:
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is elongated using "unnicked" DNA as leading strand (template);
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176:
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DNA replication systems used with small circular DNA molecules
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515:
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The molecular mechanism of
Rolling Circle Amplification (RCA)
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1084:"Viroid Replication: Rolling-Circles, Enzymes and Ribozymes"
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602:
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A suitable buffer that is compatible with the polymerase.
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978:"Viroids: an Ariadne's thread into the RNA labyrinth"
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is also widely used for the detection of RCA product.
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347:
intermediates include circular and branched circular
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Replication of both "unnicked" and displaced ssDNA.
60:. Unsourced material may be challenged and removed.
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182:As a simplified version of natural rolling circle
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480:-tethered complementary or fluorescently-labeled
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1238:Proceedings of the National Academy of Sciences
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779:Proceedings of the National Academy of Sciences
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249:removes the primer, replacing it with DNA, and
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484:. In addition to the fluorescent approaches,
323:A model for HPV16 rolling circle replication.
316:when it is packaged into individual virions.
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214:Illustration of rolling circle replication.
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773:Borenstein, Ronen; Frenkel, Niza (2009).
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120:Learn how and when to remove this message
1773:MicrobiologyBytes: Viroids and Virusoids
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545:Illustration of aptamer based immuno-rca
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1507:Angewandte Chemie International Edition
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375:Rolling circle replication of viral RNA
223:hydroxyl end is released to serve as a
202:(as a method of signal amplification).
14:
1785:
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435:Deoxynucleotide triphosphates (dNTPs)
443:The detection methods of RCA product
58:adding citations to reliable sources
29:
1778:http://mcmanuslab.ucsf.edu/node/246
24:
1721:Microsystems & Nanoengineering
391:Rolling circle amplification (RCA)
25:
1804:
1753:
1454:The American Journal of Pathology
147:) is a process of unidirectional
1597:Journal of Clinical Microbiology
1052:10.1111/j.1462-5822.2008.01231.x
851:10.1111/j.1365-2443.2010.01458.x
447:The polymerases used in RCA are
260:Circular dsDNA will be "nicked".
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609:and formation of nano-islands.
409:polymerase chain reaction (PCR)
45:needs additional citations for
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681:Demidov, Vadim V, ed. (2016).
674:
455:for DNA amplification, and T7
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1:
1466:10.1016/S0002-9440(10)61674-4
624:
521:
364:(asymmetric replication) and
198:, especially in the field of
1675:10.1371/journal.pone.0064583
955:10.1016/0022-2836(73)90443-9
742:10.1016/j.micinf.2011.03.006
69:"Rolling circle replication"
7:
612:
368:(symmetric replication).
288:
284:Displaced DNA circularizes.
10:
1809:
505:illustration of immuno-RCA
413:nucleic acid amplification
141:Rolling circle replication
1734:10.1038/micronano.2017.84
904:10.1007/s00705-014-2297-7
693:10.1007/978-3-319-42226-8
585:Other applications of RCA
581:the figure on the right.
429:A short DNA or RNA primer
1136:Chemical Society Reviews
994:10.1038/sj.embor.7400706
724:Arbuckle, Jesse (2011).
648:Chemical Society Reviews
355:Replication of viral RNA
294:Replication of viral DNA
206:Circular DNA replication
1259:10.1073/pnas.0400834101
800:10.1073/pnas.0908504106
432:A circular DNA template
411:, RCA is an isothermal
328:Human Papillomavirus-16
27:DNA synthesis technique
1765:, T. Brown et al., at
1519:10.1002/anie.200705982
1397:Nucleic Acids Research
730:Microbes and Infection
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1039:Cellular Microbiology
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227:for DNA synthesis by
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1609:10.1128/JCM.00065-14
1550:Analytical Chemistry
1358:Analytical Chemistry
1305:Nature Biotechnology
892:Archives of Virology
529:immunohistochemistry
451:, Bst, and Vent exo-
54:improve this article
1666:2013PLoSO...864583L
1409:10.1093/nar/gkaa419
1317:10.1038/nbt0402-359
1250:2004PNAS..101.4548D
791:2009PNAS..10619138B
785:(45): 19138–19143.
592:infectious diseases
497:Applications of RCA
486:gel electrophoresis
385:hammerhead ribozyme
305:human herpesvirus-6
1148:10.1039/c3cs60439j
660:10.1039/C3CS60439J
619:Selector-technique
547:
507:
445:
401:
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229:DNA polymerase III
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1562:10.1021/ac071059s
1556:(19): 7492–7500.
1513:(34): 6330–6337.
1370:10.1021/ac071059s
1364:(19): 7492–7500.
1244:(13): 4548–4553.
1142:(10): 3324–3341.
1045:(11): 2168–2179.
482:molecular beacons
276:Okazaki fragments
192:molecular biology
188:DNA amplification
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16:(Redirected from
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565:based immuno-RCA
423:A DNA polymerase
342:Bacteriophage T4
247:DNA polymerase I
186:, an isothermal
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457:RNA polymerase
453:DNA polymerase
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243:RNA polymerase
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196:nanotechnology
169:bacteriophages
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366:Avsunviroidae
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362:Pospiviroidae
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333:In addition,
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110:November 2017
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71: –
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65:Find sources:
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43:This article
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982:EMBO Reports
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946:
943:J. Mol. Biol
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891:
884:
844:(1): 23–33.
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687:. Springer.
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512:immunoassays
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349:concatemeric
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173:circular RNA
149:nucleic acid
144:
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90:
83:
76:
64:
52:Please help
47:verification
44:
1195:10.1038/898
478:fluorophore
335:geminivirus
310:concatemers
300:DNA viruses
184:replication
625:References
596:microarray
522:Immuno-RCA
251:DNA ligase
236:concatemer
200:biosensing
175:genome of
171:, and the
159:, such as
80:newspapers
1763:Genomes 2
1743:2055-7434
1727:: 17084.
1684:1932-6203
1617:0095-1137
1570:0003-2700
1527:1521-3773
1474:0002-9440
1417:0305-1048
1325:1087-0156
1268:0027-8424
1203:1546-1718
1156:1460-4744
1061:1462-5822
1035:"Viroids"
1002:1469-221X
912:0304-8608
860:1365-2443
607:nanowires
603:hydrogels
314:ribozymes
1787:Category
1702:23750210
1654:PLOS ONE
1635:24574296
1578:17722881
1535:18680110
1492:11438455
1435:32469060
1378:17722881
1343:11923841
1286:15070755
1219:21007563
1164:24643375
1120:21994552
1069:18764915
1020:16741503
928:16502010
920:25449306
876:30493728
868:21059156
819:19858479
760:21458587
711:30024718
668:24643375
613:See also
289:Virology
161:plasmids
1693:3672175
1662:Bibcode
1626:3993705
1483:1850404
1426:7367203
1334:2858761
1246:Bibcode
1211:9662393
1111:3185496
1088:Viruses
1011:1479586
963:4580243
810:2767366
787:Bibcode
751:3130849
598:assay.
563:Aptamer
514:(e.g.,
177:viroids
165:genomes
94:scholar
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471:Primer
269:5' end
265:3' end
225:primer
163:, the
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1769:Books
1215:S2CID
924:S2CID
872:S2CID
707:S2CID
516:ELISA
449:Phi29
298:Some
101:JSTOR
87:books
1767:NCBI
1739:ISSN
1698:PMID
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1613:ISSN
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1016:PMID
998:ISSN
959:PMID
916:PMID
908:ISSN
864:PMID
856:ISSN
815:PMID
756:PMID
697:ISBN
664:PMID
571:edit
263:The
73:news
1729:doi
1688:PMC
1670:doi
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1478:PMC
1462:doi
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1421:PMC
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1366:doi
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1191:doi
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951:doi
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896:160
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805:PMC
795:doi
783:106
746:PMC
738:doi
689:doi
656:doi
405:DNA
167:of
157:RNA
155:or
153:DNA
145:RCR
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