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Programmable and multiparameter DNA-based logic platform for cancer recognition and targeted therapy.

You M, Zhu G, Chen T, Donovan MJ, Tan W - J. Am. Chem. Soc. (2014)

Bottom Line: The specific inventory of molecules on diseased cell surfaces (e.g., cancer cells) provides clinicians an opportunity for accurate diagnosis and intervention.With the discovery of panels of cancer markers, carrying out analyses of multiple cell-surface markers is conceivable.The success of this strategy demonstrates the potential of DNA nanotechnology in facilitating targeted disease diagnosis and effective therapy.

View Article: PubMed Central - PubMed

Affiliation: Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Collaborative Innovation Center for Molecular Engineering and Theranostics, Hunan University , Changsha, Hunan 410082, China.

ABSTRACT
The specific inventory of molecules on diseased cell surfaces (e.g., cancer cells) provides clinicians an opportunity for accurate diagnosis and intervention. With the discovery of panels of cancer markers, carrying out analyses of multiple cell-surface markers is conceivable. As a trial to accomplish this, we have recently designed a DNA-based device that is capable of performing autonomous logic-based analysis of two or three cancer cell-surface markers. Combining the specific target-recognition properties of DNA aptamers with toehold-mediated strand displacement reactions, multicellular marker-based cancer analysis can be realized based on modular AND, OR, and NOT Boolean logic gates. Specifically, we report here a general approach for assembling these modular logic gates to execute programmable and higher-order profiling of multiple coexisting cell-surface markers, including several found on cancer cells, with the capacity to report a diagnostic signal and/or deliver targeted photodynamic therapy. The success of this strategy demonstrates the potential of DNA nanotechnology in facilitating targeted disease diagnosis and effective therapy.

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Construction of programmable and scalable cell-surfacelogic machines.The realization of (A) four-input “a AND b AND c AND d”gate, and (B) four-input “a AND b AND d NOT c” gate.The fluorescence intensity results in the truth table were based onaveraged flow cytometry distributions, from three experiments. Bracketedletter-labeled strand (e.g., [d] strand) is complementary to the strandlabeled with the same letter (e.g., d strand).
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fig4: Construction of programmable and scalable cell-surfacelogic machines.The realization of (A) four-input “a AND b AND c AND d”gate, and (B) four-input “a AND b AND d NOT c” gate.The fluorescence intensity results in the truth table were based onaveraged flow cytometry distributions, from three experiments. Bracketedletter-labeled strand (e.g., [d] strand) is complementary to the strandlabeled with the same letter (e.g., d strand).

Mentions: To demonstrate the modularity and scalabilityof DNA-based approachesthat are similarly based on the rational tagging of specific barcodetags to the cell-targeting aptamers, we proved the successful operationof another 10 three-input logic gates (Figure 3) and 2 four-input systems, “Sgc8c AND Sgc4f AND TE17 ANDTC01” and “Sgc8c AND Sgc4f AND TC01 AND-NOT TE17”(Figure 4). The detailed experimental schemesfor individual gates are displayed in Figure S7, in which both a targeted therapeutic effect and a cell surfacefluorescence signal from flow cytometry proved the proper functionof the logic device.


Programmable and multiparameter DNA-based logic platform for cancer recognition and targeted therapy.

You M, Zhu G, Chen T, Donovan MJ, Tan W - J. Am. Chem. Soc. (2014)

Construction of programmable and scalable cell-surfacelogic machines.The realization of (A) four-input “a AND b AND c AND d”gate, and (B) four-input “a AND b AND d NOT c” gate.The fluorescence intensity results in the truth table were based onaveraged flow cytometry distributions, from three experiments. Bracketedletter-labeled strand (e.g., [d] strand) is complementary to the strandlabeled with the same letter (e.g., d strand).
© Copyright Policy - editor-choice
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4308741&req=5

fig4: Construction of programmable and scalable cell-surfacelogic machines.The realization of (A) four-input “a AND b AND c AND d”gate, and (B) four-input “a AND b AND d NOT c” gate.The fluorescence intensity results in the truth table were based onaveraged flow cytometry distributions, from three experiments. Bracketedletter-labeled strand (e.g., [d] strand) is complementary to the strandlabeled with the same letter (e.g., d strand).
Mentions: To demonstrate the modularity and scalabilityof DNA-based approachesthat are similarly based on the rational tagging of specific barcodetags to the cell-targeting aptamers, we proved the successful operationof another 10 three-input logic gates (Figure 3) and 2 four-input systems, “Sgc8c AND Sgc4f AND TE17 ANDTC01” and “Sgc8c AND Sgc4f AND TC01 AND-NOT TE17”(Figure 4). The detailed experimental schemesfor individual gates are displayed in Figure S7, in which both a targeted therapeutic effect and a cell surfacefluorescence signal from flow cytometry proved the proper functionof the logic device.

Bottom Line: The specific inventory of molecules on diseased cell surfaces (e.g., cancer cells) provides clinicians an opportunity for accurate diagnosis and intervention.With the discovery of panels of cancer markers, carrying out analyses of multiple cell-surface markers is conceivable.The success of this strategy demonstrates the potential of DNA nanotechnology in facilitating targeted disease diagnosis and effective therapy.

View Article: PubMed Central - PubMed

Affiliation: Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Collaborative Innovation Center for Molecular Engineering and Theranostics, Hunan University , Changsha, Hunan 410082, China.

ABSTRACT
The specific inventory of molecules on diseased cell surfaces (e.g., cancer cells) provides clinicians an opportunity for accurate diagnosis and intervention. With the discovery of panels of cancer markers, carrying out analyses of multiple cell-surface markers is conceivable. As a trial to accomplish this, we have recently designed a DNA-based device that is capable of performing autonomous logic-based analysis of two or three cancer cell-surface markers. Combining the specific target-recognition properties of DNA aptamers with toehold-mediated strand displacement reactions, multicellular marker-based cancer analysis can be realized based on modular AND, OR, and NOT Boolean logic gates. Specifically, we report here a general approach for assembling these modular logic gates to execute programmable and higher-order profiling of multiple coexisting cell-surface markers, including several found on cancer cells, with the capacity to report a diagnostic signal and/or deliver targeted photodynamic therapy. The success of this strategy demonstrates the potential of DNA nanotechnology in facilitating targeted disease diagnosis and effective therapy.

Show MeSH
Related in: MedlinePlus