An ideal clinical assay for detecting circulating tumor cells should be high throughput (as simple as a one-step reaction) and highly sensitive (requiring as little as one drop of blood). The current assay to detect circulating tumor cells is time- and labor-consuming multi-step procedure, requiring isolation of tumor cells, staining with antibodies, and repeated washes to reduce background. To overcome these obstacles, we have developed a unique aptamer probe that carries a """"""""tumor cell-activatable"""""""" reporting system. The aptamer probes specifically bind tumor biomarker(s) and are optically silent in the absence of target cells, thus giving no to minimal background. To translate these research findings to the clinic, the goal of this study is to develop a novel technology for circulating tumor cell detectio in a """"""""One-Drop (of blood)-One-Step Assay"""""""" (ODOSA).
The specific aims of this proposal are to: 1. Optimize sensitivity and specificity of the aptamer probes for the ODOSA technology;2. Develop a multi-sample and high-throughput platform for the ODOSA technology;and 3. Validate the ODOSA technology in clinical specimens. Scientifically, this study presents an innovative concept that tumor cells can be specifically detected by activating the aptamer probes through a natural cellular process with exclusively intracellular signals and no background. Technically, the ODOSA is a technological breakthrough over the current antibody-mediated assays. Clinically, the ODOSA provides a high- throughput and multi-sample platform, and enables physicians to detect one single circulating tumor cell among millions of cells in real time using a minimal amount of blood. There is no alternative clinical assay available to date.

Public Health Relevance

The proposed One-Drop (of blood)-One-Step Assay (ODOSA) presents transformative technological advance that would allow physicians to detect various circulating cancers in one drop of a patient's blood. The current antibody-mediated process is labor and time intensive, with multiple steps requiring large initial sample volumes. The proposed ODOSA is a technological breakthrough. Clinical implementation of the ODOSA would enable early detection and accurate monitoring of therapeutic response of cancer tumors.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants Phase II (R33)
Project #
5R33CA173382-02
Application #
8547047
Study Section
Special Emphasis Panel (ZCA1-SRLB-4 (O1))
Program Officer
Sorbara, Lynn R
Project Start
2012-09-18
Project End
2015-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
2
Fiscal Year
2013
Total Cost
$358,529
Indirect Cost
$127,964
Name
Methodist Hospital Research Institute
Department
Type
DUNS #
185641052
City
Houston
State
TX
Country
United States
Zip Code
77030
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Yu, Ge; Li, Huan; Yang, Shuanghui et al. (2016) ssDNA Aptamer Specifically Targets and Selectively Delivers Cytotoxic Drug Doxorubicin to HepG2 Cells. PLoS One 11:e0147674
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Sun, Hongguang; Zu, Youli (2015) Aptamers and their applications in nanomedicine. Small 11:2352-64
Choi, Dong Soon; Stark, Daniel J; Raphael, Robert M et al. (2015) SDF-1? stiffens myeloma bone marrow mesenchymal stromal cells through the activation of RhoA-ROCK-Myosin II. Int J Cancer 136:E219-29

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