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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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Related in: MedlinePlus

Schemes of the cell-surface logic gates.(A) General principledisplayed using two-input “AND” gate as an example.Target cell expressing both membrane receptors (blue and red) canbe selected for labeling or apoptosis (red circled cell). Tagged aptamerprobes are first incubated with cells, after washing and discardingthe nonbinding probes, dye or drug-labeled reporter probe or duplexis added, and the final cellular fluorescence signal or cellular viabilityis detected with a FACScan cytometer or PI staining assay. (B) Symbols,truth tables, and experimental schemes of toehold-based strand displacement“AND” gate.
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fig1: Schemes of the cell-surface logic gates.(A) General principledisplayed using two-input “AND” gate as an example.Target cell expressing both membrane receptors (blue and red) canbe selected for labeling or apoptosis (red circled cell). Tagged aptamerprobes are first incubated with cells, after washing and discardingthe nonbinding probes, dye or drug-labeled reporter probe or duplexis added, and the final cellular fluorescence signal or cellular viabilityis detected with a FACScan cytometer or PI staining assay. (B) Symbols,truth tables, and experimental schemes of toehold-based strand displacement“AND” gate.

Mentions: The logic device is based onBoolean operations as shown in Figure 1 andconsists of two types of components.19 Thefirst is a short oligonucleotide tag connected to a specific aptamerprobe. Different aptamers may have the same or different tags, andthese tags act as barcodes that reflect the cell profiling results.The second component serves as a barcode reader and actuator, witheither fluorophore- or therapeutic reagent-labeled ssDNA or dsDNA,whose sequences are designed based on the barcode tags just described.As a result, the actuator can screen the presence or absence of differentbiological markers on the cell surface and take action after appropriatelydiscriminating the expression patterns of these markers. These twocomponents are not physically linked with each other; instead, theyare operationally connected. That is, while the aptamers functionallybind to their cognate cell membrane targets, the tags and actuatorsfunctionally execute the logic operations (conjunction, disjunction,negation) based on such recognition.


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)

Schemes of the cell-surface logic gates.(A) General principledisplayed using two-input “AND” gate as an example.Target cell expressing both membrane receptors (blue and red) canbe selected for labeling or apoptosis (red circled cell). Tagged aptamerprobes are first incubated with cells, after washing and discardingthe nonbinding probes, dye or drug-labeled reporter probe or duplexis added, and the final cellular fluorescence signal or cellular viabilityis detected with a FACScan cytometer or PI staining assay. (B) Symbols,truth tables, and experimental schemes of toehold-based strand displacement“AND” gate.
© Copyright Policy - editor-choice
Related In: Results  -  Collection

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

fig1: Schemes of the cell-surface logic gates.(A) General principledisplayed using two-input “AND” gate as an example.Target cell expressing both membrane receptors (blue and red) canbe selected for labeling or apoptosis (red circled cell). Tagged aptamerprobes are first incubated with cells, after washing and discardingthe nonbinding probes, dye or drug-labeled reporter probe or duplexis added, and the final cellular fluorescence signal or cellular viabilityis detected with a FACScan cytometer or PI staining assay. (B) Symbols,truth tables, and experimental schemes of toehold-based strand displacement“AND” gate.
Mentions: The logic device is based onBoolean operations as shown in Figure 1 andconsists of two types of components.19 Thefirst is a short oligonucleotide tag connected to a specific aptamerprobe. Different aptamers may have the same or different tags, andthese tags act as barcodes that reflect the cell profiling results.The second component serves as a barcode reader and actuator, witheither fluorophore- or therapeutic reagent-labeled ssDNA or dsDNA,whose sequences are designed based on the barcode tags just described.As a result, the actuator can screen the presence or absence of differentbiological markers on the cell surface and take action after appropriatelydiscriminating the expression patterns of these markers. These twocomponents are not physically linked with each other; instead, theyare operationally connected. That is, while the aptamers functionallybind to their cognate cell membrane targets, the tags and actuatorsfunctionally execute the logic operations (conjunction, disjunction,negation) based on such recognition.

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