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Generation of Cell-Specific Aptamers in Oncology
Thursday, 9 March 2017
Generation of Cell-Specific Aptamers in Oncology
Aptamers are single stranded DNA or RNA oligonucleotides, ~30 - 80 bases in length, that form three-dimensional structures that can selectively bind to specific targets. Variations on the traditional SELEXTM aptamer selection process utilizing postoperative tissues and modified cells are being employed to develop highly selective aptamers for potential use in cancer diagnostics and therapeutics.
A team of researchers at the Krasnoyarsk State Medical University, Krasnoyarsk Research Center, and the Krasnoyarsk Regional Clinical Cancer Center in Russia and researchers at the University of Ottawa, Canada developed aptamers selective for lung cancer cells. Lung adenocarcinoma cells were isolated from post-operative tissue for positive selection. Healthy lung tissue from the same donors and whole blood from healthy donors were used for negative selection. Degree of enhanced binding to adenocarcinoma cells vs. controls was used to choose the final aptamer sequences. Using LC-MS analysis, potential protein targets were identified for each selected aptamer. Because individual aptamer sequences specific for lung cancer cells were shown to bind different cell surface markers, a pool of aptamer clones may offer enhanced detection. Taking a personalized medicine approach, the researchers suggest that tumor-specific aptamers could be produced for individual patients. The blood smear technique developed would facilitate tumor monitoring during treatment. Aptamers to specific cell types can be generated without prior knowledge of cell surface markers – particularly useful when working with a high degree of variability in surface marker expression. (2)
The researchers at Krasnoyarsk also utilized post-operative breast tissue to generate aptamers selective for breast cancer cells and tissue. This tissue-based SELEXTM utilized positive selection based on malignant tumor tissue from 11 patients. Negative selection utilized benign tumor tissue from 8 donors, lung cancer tissue samples, a glioblastoma tissue sample, and healthy breast tissue. DNA aptamers selective for breast cancer cells may be utilized to identify new diagnostic biomarkers and targets for therapy and to enable targeted delivery of anti-cancer drugs. (3)
Pancreatic cancer is often diagnosed at an advanced stage where there is little chance of effective treatment. Based on findings related to the role of cancer stem cells (CSCs) in the pathogenesis of cancer, researchers at the Yonsei University College of Medicine in Seoul, South Korea developed aptamers selective for circulating pancreatic tumor cells exhibiting the characteristics of cancer stem cells. In order to generate aptamers with this unique selectivity, researchers utilized the sphere-forming property of stem cells. Positive selection was performed with dissociated sphere cells generated from HPAC human pancreatic adenocarcinoma cells. Following aptamer selection, aptamer-binding cells showed a high level of CSC-related genes and expression of CSC-related cell surface markers, confirming specificity. Aptamer binding was actually shown to be co-localized with CD133, a rare surface marker in HPAC cells. Aptamers selective for stem cell-enriched circulating tumor cells may someday enable earlier diagnosis, via non-invasive screening, or be effective as direct therapeutic or drug targeting agents in the treatment of pancreatic cancer. (1)
Aptamers offer exciting opportunities in the field of oncology for diagnosis, biomarker / target discovery, therapeutics, and targeted drug delivery. The development of more sensitive, non-invasive screening methods is a first step in the application of aptamers as a new tool in the ongoing effort to treat a wide range of cancers.
References:
1. Kim, Y.J., Lee, H. S., Jung, D. E., Kim, J. M., and Song, S. Y. (2016), The DNA aptamer binds
stemness-enriched cancer cells in pancreatic cancer. J Mol. Recognit. doi: 10.1002/jmr.2591
2. Zamay, G.S. et al. (2015) Aptamers selected to postoperative lung adenocarcinoma detect circulating tumor cells in human blood. Molecular Therapy. 23(9):1486-96. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4817883/pdf/mt2015108a.pdf
3. Zamay, G. S. et al. (2016) Selection of DNA aptamers for breast cancer. Biochemistry (Moscow)
Supplement Series B: Biomedical Chemistry. 10:2, 158-164.
doi: 10.1134/S1990750816020128
Article Source:
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