Catalytic Molecular Beacons

Stojanović, Milan N.; Prada, Paloma de; Landry, Donald W.

doi:10.1002/1439-7633(20010601)2:6<411::aid-cbic411>3.0.co;2-i

Cited by 133 publications

(46 citation statements)

References 24 publications

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“…Our first result that was reported in peer-reviewed literature was a modular design, 15 called either a catalytic molecular beacon 18 when sensitive to one oligonucleotide or a gate (Figure 1) when sensitive to one or more oligonucleotides. 3,18 In these, the catalytic activity of a deoxyribozyme 19 module is controlled by up to three oligonucleotide inputs through recognition modules based on molecular beacons.…”

Section: Developing Deoxyribozyme-based Logic Gates and Their Circuitsmentioning

confidence: 99%

“…3,18 In these, the catalytic activity of a deoxyribozyme 19 module is controlled by up to three oligonucleotide inputs through recognition modules based on molecular beacons. 20 When active, the deoxyribozyme has phosphodiesterase activity and cleaves another oligonucleotide, 18 the substrate, and this cleavage is the output of the gate. By labeling the substrate fluorogenically, we can monitor the progress of the cleavage via an increase of fluorescence.…”

Section: Developing Deoxyribozyme-based Logic Gates and Their Circuitsmentioning

confidence: 99%

“…(a) An example of deoxyribozyme ( E6 18 ) shown in complex with its substrate ( S T ). The cleavage reaction of S T produces two shorter products ( P Q and P T ) as output ( O ); output production can be monitored by fluorogenic cleavage ( BH 2 is black hole quencher, while T is fluorescent dye carboxytetramethylrhodamine, TAMRA).…”

Section: Developing Deoxyribozyme-based Logic Gates and Their Circuitsmentioning

confidence: 99%

“…We use a single stem–loop region to block access of the substrate to the deoxyribozyme’s substrate recognition region (Figure 1c, YESi 1 ), which results in a YES gate 18 (i.e., a signal detector or repeater or basic catalytic molecular beacon). When the oligonucleotide complementary to the loop is present, it binds to the loop, opening the stem and thus allowing the substrate to bind to the deoxyribozyme, whereupon it is cleaved.…”

Section: Developing Deoxyribozyme-based Logic Gates and Their Circuitsmentioning

confidence: 99%

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Exercises in Molecular Computing

2014

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ConspectusThe successes of electronic digital logic have transformed every aspect of human life over the last half-century. The word “computer” now signifies a ubiquitous electronic device, rather than a human occupation. Yet evidently humans, large assemblies of molecules, can compute, and it has been a thrilling challenge to develop smaller, simpler, synthetic assemblies of molecules that can do useful computation. When we say that molecules compute, what we usually mean is that such molecules respond to certain inputs, for example, the presence or absence of other molecules, in a precisely defined but potentially complex fashion. The simplest way for a chemist to think about computing molecules is as sensors that can integrate the presence or absence of multiple analytes into a change in a single reporting property. Here we review several forms of molecular computing developed in our laboratories.When we began our work, combinatorial approaches to using DNA for computing were used to search for solutions to constraint satisfaction problems. We chose to work instead on logic circuits, building bottom-up from units based on catalytic nucleic acids, focusing on DNA secondary structures in the design of individual circuit elements, and reserving the combinatorial opportunities of DNA for the representation of multiple signals propagating in a large circuit. Such circuit design directly corresponds to the intuition about sensors transforming the detection of analytes into reporting properties. While this approach was unusual at the time, it has been adopted since by other groups working on biomolecular computing with different nucleic acid chemistries.We created logic gates by modularly combining deoxyribozymes (DNA-based enzymes cleaving or combining other oligonucleotides), in the role of reporting elements, with stem–loops as input detection elements. For instance, a deoxyribozyme that normally exhibits an oligonucleotide substrate recognition region is modified such that a stem–loop closes onto the substrate recognition region, making it unavailable for the substrate and thus rendering the deoxyribozyme inactive. But a conformational change can then be induced by an input oligonucleotide, complementary to the loop, to open the stem, allow the substrate to bind, and allow its cleavage to proceed, which is eventually reported via fluorescence. In this Account, several designs of this form are reviewed, along with their application in the construction of large circuits that exhibited complex logical and temporal relationships between the inputs and the outputs.Intelligent (in the sense of being capable of nontrivial information processing) theranostic (therapy + diagnostic) applications have always been the ultimate motivation for developing computing (i.e., decision-making) circuits, and we review our experiments with logic-gate elements bound to cell surfaces that evaluate the proximal presence of multiple markers on lymphocytes.

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Section: Developing Deoxyribozyme-based Logic Gates and Their Circuitsmentioning

confidence: 99%

Section: Developing Deoxyribozyme-based Logic Gates and Their Circuitsmentioning

confidence: 99%

Section: Developing Deoxyribozyme-based Logic Gates and Their Circuitsmentioning

confidence: 99%

Section: Developing Deoxyribozyme-based Logic Gates and Their Circuitsmentioning

confidence: 99%

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Exercises in Molecular Computing

2014

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“…If we hook two NOT gates together we will now have a YES gate or non-inverting buffer) consists of an inactive deoxyribozyme module (ST) and another attached beacon module. 33, 34 The output signal can be realized when the ST region is cleaved based on the following steps. First, the input sequence opens the loop of the beacon module and releases its stem.…”

Section: Rational Design Of Nucleic Acid Molecular Logic Systemmentioning

confidence: 99%

A survey of advancements in nucleic acid-based logic gates and computing for applications in biotechnology and biomedicine

Wan

Hou

et al. 2015

Chem. Commun.

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Nucleic acid-based logic devices were first introduced in 1994. Since then, science has seen the emergence of new logic systems for mimicking mathematical functions, diagnosing disease and even imitating biological systems. The unique features of nucleic acids, such as facile and high-throughput synthesis, Watson-Crick complementary base pairing, and predictable structures, together with the aid of programming design, have led to the widespread applications of nucleic acids (NA) for logic gating and computing in biotechnology and biomedicine. In this feature article, the development of in vitro NA logic systems will be discussed, as well as the expansion of such systems using various input molecules for potential cellular, or even in vivo, applications.

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