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.
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.
|Liang, Li; Jiang, Yi; Chen, Jun-Song et al. (2016) B7-H4 expression in ovarian serous carcinoma: a study of 306 cases. Hum Pathol 57:1-6|
|Sun, Hongguang; Tan, Weihong; Zu, Youli (2016) Aptamers: versatile molecular recognition probes for cancer detection. Analyst 141:403-15|
|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|
|Sun, Hongguang; Zu, Youli (2015) Aptamers and their applications in nanomedicine. Small 11:2352-64|
|Wen, Jianguo; Tao, Wenjing; Kuiatse, Isere et al. (2015) Dynamic balance of multiple myeloma clonogenic side population cell percentages controlled by environmental conditions. Int J Cancer 136:991-1002|
|Choi, Dong Soon; Stark, Daniel J; Raphael, Robert M et al. (2015) SDF-1Î± stiffens myeloma bone marrow mesenchymal stromal cells through the activation of RhoA-ROCK-Myosin II. Int J Cancer 136:E219-29|
|Sun, Hongguang; Zu, Youli (2015) A Highlight of Recent Advances in Aptamer Technology and Its Application. Molecules 20:11959-80|
|Zhao, Nianxi; Pei, Sung-Nan; Qi, Jianjun et al. (2015) Oligonucleotide aptamer-drug conjugates for targeted therapy of acute myeloid leukemia. Biomaterials 67:42-51|
|Zhao, Nianxi; Pei, Sung-nan; Parekh, Parag et al. (2014) Blocking interaction of viral gp120 and CD4-expressing T cells by single-stranded DNA aptamers. Int J Biochem Cell Biol 51:10-8|
|Wen, Jianguo; Li, Hangwen; Tao, Wenjing et al. (2014) High throughput quantitative reverse transcription PCR assays revealing over-expression of cancer testis antigen genes in multiple myeloma stem cell-like side population cells. Br J Haematol 166:711-9|
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