Evaluation of intracellular telomerase activity through cascade DNA logic gates

Wang, Wenjing; Huang, Shan; Li, Jingjing; Rui, Kai; Bi, Sai; Zhang, Jianrong; Zhu, Jun‐Jie

doi:10.1039/c6sc01953f

Cited by 61 publications

(39 citation statements)

References 35 publications

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“…We finally investigated where our DNA probes were located and functioned in live cells. Costaining with 4,6‐diamino‐2‐phenylindole (DAPI) indicated that O1 and S2 were mainly distributed around the nucleus (Figure S12); thus suggesting high telomerase activity in the cytoplasm of cancer cells, which is identical to that previously reported . It is supposed that, if telomerase can trigger hairpin formation of S2 , the extended S2 will form a framework that contains multiple TTAGGG repeats.…”

Section: Resultssupporting

confidence: 77%

Live‐Cell Sensing of Telomerase Activity by Using Hybridization‐Sensitive Fluorescent Oligonucleotide Probes

et al. 2019

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Live‐cell sensing of telomerase activity with simple and efficient strategies remains a challenging target. In this work, a strategy for telomerase sensing by using hybridization‐sensitive fluorescent oligonucleotide probes is reported. In the presence of telomerase and dNTPs, the designed supporting strand was extended and generated the hairpin structure that catalyzed the next telomerase extending reaction. The special extension mechanism increased the local concentration of another supporting strand and telomerase, which resulted in enhanced telomerase activity. The hybridization‐sensitive oligonucleotide probes bound to the hairpin catalyst and generated turn‐on fluorescence. This method realized the sensing of telomerase activity in HeLa cell extract with a detection limit below 1.6×10−6 IU μL−1. The real‐time in situ observation of telomerase extension was achieved in living HeLa cells. This strategy has been applied to monitor the efficiency of telomerase‐targeting anticancer drugs in situ.

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Section: Resultssupporting

confidence: 77%

Live‐Cell Sensing of Telomerase Activity by Using Hybridization‐Sensitive Fluorescent Oligonucleotide Probes

et al. 2019

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“…In this step, the behavior of FNA‐1 is consistent with an AND‐gate that is connected to the first OR‐gate. Taken as a whole, FNA‐1 in fact behaves as a logic circuit consisting of two cascaded logic gates (OR‐AND), of which the truth table and logic symbol are shown in Figure a (right panel) and Figure c, respectively. In contrast to FNA‐1, the control structure C‐FNA (Supporting Information, Figure S6) does not respond to external stimuli in all cases, consistent with the PAGE results.…”

Section: Resultsmentioning

confidence: 99%

Environment‐Recognizing DNA‐Computation Circuits for the Intracellular Transport of Molecular Payloads for mRNA Imaging

et al. 2020

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Programming intelligent DNA nanocarriers for the targeted transport of molecular payloads in living cells has attracted extensive attention. In vivo activation of these nanocarriers usually relies on external light irradiation. An interest is emerging in the automatic recognition of intracellular surroundings by nanocarriers and their in situ activation under the control of programmed DNA‐computation circuits. Herein, we report the integration of DNA circuits with framework nucleic acid (FNA) nanocarriers that consist of a truncated square pyramid (TSP) cage and a built‐in duplex cargo containing an antisense strand of the target mRNA. An i‐motif and ATP aptamer embedded in the TSP are employed as logic‐controlling units to respond to H+ and ATP inside cellular compartments, triggering the release of the sensing element for fluorescent mRNA imaging. Logic‐controlled FNA devices could be used to target drug delivery, enabling precise disease treatment.

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“…[10,37] Since the strand-displacementr eaction can be easily cascaded and mimics the wire function in digital electronics, some logic devices werea lso developed based on the spontaneousDNA reaction. [38] Zhang and Zhu et al [39] constructed ac ascade nucleic acid logic gate that responded to intracellular telomerase and applied it in imaging intracellulart elomerase activity.T hey de-signedaDNA computation system that includes a TS probe, which is the telomerase substrate primer, at oehold-bearing DNA duplex that consists of a G T strand,afluorophore-modified G F strand and aq uencher-modified G Q strand,a nd Input B,w hich is the partial-complementary strand of G F .F irstly,t he TS probe could be extended by telomerase with repetitive sequences of TTAGGG,f orming TS + nR strand (Figure4i). The TS + nR strand could recognize and hybridize with the toehold domain of the duplex (G T -G F -G Q )t oi nitiate spontaneous strand migration and displacement,t hereby separating the flu- .…”

Section: Signals Derivedf Rom Strand-displacement Reactionsmentioning

confidence: 99%

“…Zhang and Zhu et al . constructed a cascade nucleic acid logic gate that responded to intracellular telomerase and applied it in imaging intracellular telomerase activity.…”

Section: Basic Signal Strategies Based On Dna Structuresmentioning

confidence: 99%

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Recent Progress in Fluorescence Signal Design for DNA‐Based Logic Circuits

Yang

Song

et al. 2019

Chemistry A European J

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DNA‐based logic circuits, encoding algorithms in DNA and processing information, are pushing the frontiers of molecular computers forward, owing to DNA′s advantages of stability, accessibility, manipulability, and especially inherent biological significance and potential medical application. In recent years, numerous logic functions, from arithmetic to nonarithmetic, have been realized based on DNA. However, DNA can barely provide a detectable signal by itself, so that the DNA‐based circuits depend on extrinsic signal actuators. The signal strategy of carrying out a response is becoming one of the design focuses in DNA‐based logic circuit construction. Although work on sequence and structure design for DNA‐based circuits has been well reviewed, the strategy on signal production lacks comprehensive summary. In this review, we focused on the latest designs of fluorescent output for DNA‐based logic circuits. Several basic strategies are summarized and a few designs for developing multi‐output systems are provided. Finally, some current difficulties and possible opportunities were also discussed.

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Evaluation of intracellular telomerase activity through cascade DNA logic gates

Abstract: DNA computation allowed the imaging of intracellular telomerase and enabled the differentiation of cancer cell lines and normal cell lines.

Cited by 61 publications

References 35 publications

Live‐Cell Sensing of Telomerase Activity by Using Hybridization‐Sensitive Fluorescent Oligonucleotide Probes

Live‐Cell Sensing of Telomerase Activity by Using Hybridization‐Sensitive Fluorescent Oligonucleotide Probes

Environment‐Recognizing DNA‐Computation Circuits for the Intracellular Transport of Molecular Payloads for mRNA Imaging

Recent Progress in Fluorescence Signal Design for DNA‐Based Logic Circuits

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