Abnormal scar identification with spherical-nucleic-acid technology

Yeo, David; Wiraja, Christian; Paller, Amy S.; Mirkin, Chad A.; Xu, Chen

doi:10.1038/s41551-018-0218-x

Cited by 71 publications

(104 citation statements)

References 43 publications

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“…CTGF mRNA and TGFβRI were chosen as targets for detection and mRNA regulation, respectively. CTGF mRNA is highly expressed in HSFs and has been shown to be a suitable biomarker, while TGFβRI siRNA targets the upstream receptor TGFβRI and has been shown to be an efficient in vivo CTGF mRNA suppression…”

Section: Resultsmentioning

confidence: 99%

“…Abnormal expression of mRNA tends to precede the cutaneous features of scars and can provide a target for earlier treatment, potentially averting the permanent sequelae . Providing specific and sensitive probes, the temporal and spatial distribution of mRNA at the cellular level can be monitored in a quantitative and non‐invasive way, which would allow us to identify the abnormal fibroblasts in the skin of live mice and rabbits, and to ex vivo human skin models …”

Section: Introductionmentioning

confidence: 99%

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Oligonucleotide Molecular Sprinkler for Intracellular Detection and Spontaneous Regulation of mRNA for Theranostics of Scar Fibroblasts

Zheng

Wiraja

Yeo

et al. 2018

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Early diagnosis and timely intervention are key for the successful treatment of skin diseases like abnormal scars. This study introduces a nucleic‐acid‐based probe (i.e., molecular sprinkler) for the diagnosis and spontaneous regulation of the abnormal expression of fibrosis‐related mRNA in scar‐derived skin fibroblasts. Using mRNA encoding connective tissue growth factor (CTGF) as the model gene, a probe with three oligonucleotides is constructed, including a recognition sequence complementary to the CTGF mRNA, a siRNA against transforming growth factor receptor I (TGFβRI) as the CTGF mRNA suppressor, and a connecting sequence. The probe can detect CTGF mRNA with a limit of 10 × 10−9 m and distinguishes scar fibroblasts from normal ones in both 2D and 3D environments. Two days after transfection, the siRNA released from the probe reduces the expression of TGFβRI and, consequently, decreases the cellular expression of CTGF mRNA (up to 70%). This dual‐role probe presents opportunities to monitor the TGF‐ β signaling pathway, screen for drugs that target the CTGF pathway, and determine the role of inhibition of the CTGF pathway in therapeutic efficacy.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Oligonucleotide Molecular Sprinkler for Intracellular Detection and Spontaneous Regulation of mRNA for Theranostics of Scar Fibroblasts

Zheng

Wiraja

Yeo

et al. 2018

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“…Recently, NanoFlares have been used for numerous applications ex vivo and in vivo. For instance, Yeo et al utilized NanoFlares for abnormal scar detection . The connective tissue growth factor (CTGF) mRNA is overexpressed in incidences of hypertrophic and keloidal scars, resulting in overproduction of collagen.…”

Section: Hybridization‐based Probesmentioning

confidence: 99%

Nucleic‐Acid Structures as Intracellular Probes for Live Cells

2019

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The chemical composition of cells at the molecular level determines their growth, differentiation, structure, and function. Probing this composition is powerful because it provides invaluable insight into chemical processes inside cells and in certain cases allows disease diagnosis based on molecular profiles. However, many techniques analyze fixed cells or lysates of bulk populations, in which information about dynamics and cellular heterogeneity is lost. Recently, nucleic‐acid‐based probes have emerged as a promising platform for the detection of a wide variety of intracellular analytes in live cells with single‐cell resolution. Recent advances in this field are described and common strategies for probe design, types of targets that can be identified, current limitations, and future directions are discussed.

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“…In our study, involving a NanoFlare that was responsive to connective tissue growth factor (CTGF) mRNA (i.e., with fluorescence flare strands that were detachable upon mRNA hybridization, Figure A), such penetration ability was found on the skin of live mice and rabbits, as well as on ex vivo human skin (Figure B). Furthermore, fluorescence specificity facilitated correlation with the quantity of hypertrophic scar‐derived fibroblast (HSF) cells, enabling a biopsy‐free scar diagnosis and potentially allowing disease monitoring as well as gauging treatment response through longitudinal observation (Figure C) …”

Section: Nucleic‐acid‐based Sensors For Functional Gene Monitoringmentioning

confidence: 99%

“…With the exception of a number of works involving aptamer‐tumour targeting and inducible formulation disassembly for drug release/signal generation, our NanoFlare study is the first to report the use of a topically applied NA sensor to diagnose skin diseases through biomarker imaging. Promisingly, we showed that the probe signal from CTGF NanoFlares correlated well with the “scar elevation index”, a functional measure of abnormal scarring in a rabbit wound scarring model . Moving forward, further in situ diagnosis applications are to be expected, through clever adaptation of new or previously proposed NA sensors alongside multidisciplinary efforts from clinicians, scientists and engineers to meet and solve current limitations described above.…”

Section: Perspectives Of Na Sensors For In Situ Diagnosismentioning

confidence: 99%

Functional Imaging with Nucleic‐Acid‐Based Sensors: Technology, Application and Future Healthcare Prospects

et al. 2018

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Timely monitoring and assessment of human health plays a crucial role in maintaining the wellbeing of our advancing society. In addition to medical tools and devices, suitable probe agents are crucial to assist such monitoring, either in passive or active ways (i.e., sensors) through inducible signals. In this review we highlight recent developments in activatable optical sensors based on nucleic acids. Sensing mechanisms and bio-applications of these nucleic acid sensors in ex vivo assays, intracellular or in vivo settings are described. In addition, we discuss the limitations of these sensors and how nanotechnology can complement/enhance sensor properties to promote translation into clinical applications.

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Abnormal scar identification with spherical-nucleic-acid technology

Cited by 71 publications

References 43 publications

Oligonucleotide Molecular Sprinkler for Intracellular Detection and Spontaneous Regulation of mRNA for Theranostics of Scar Fibroblasts

Oligonucleotide Molecular Sprinkler for Intracellular Detection and Spontaneous Regulation of mRNA for Theranostics of Scar Fibroblasts

Nucleic‐Acid Structures as Intracellular Probes for Live Cells

Functional Imaging with Nucleic‐Acid‐Based Sensors: Technology, Application and Future Healthcare Prospects

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