Genetic Alphabet Expansion Provides Versatile Specificities and Activities of Unnatural-base DNA Aptamers Targeting Cancer Cells

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Genetic Alphabet Expansion Provides Versatile Specificities and Activities of Unnatural-base DNA Aptamers Targeting Cancer Cells
Title:
Genetic Alphabet Expansion Provides Versatile Specificities and Activities of Unnatural-base DNA Aptamers Targeting Cancer Cells
Other Titles:
Molecular Therapy Nucleic Acids
Publication Date:
28 November 2018
Citation:
Genetic Alphabet Expansion Provides Versatile Specificities and Activities of Unnatural-Base DNA Aptamers Targeting Cancer Cells Futami, Kazunobu et al. Molecular Therapy - Nucleic Acids, Volume 14, 158 - 170
Abstract:
The potential of genetic alphabet expansion technologies using artificial extra base pairs (unnatural base pairs) has been rapidly expanding and increasing. We present that the hydrophobic unnatural base, 7-(2-thienyl)imidazo[4,5-b]pyridine (Ds), which acts as a fifth letter in a DNA library, provides a series of high-affinity DNA aptamers with versatile binding specificities and activities to cancer cells. These Ds-containing DNA aptamers were generated by a method called cell-ExSELEX, to target three breast cancer cell lines, MCF7, MDA-MB-231, and T-47D. Aptamer 14A-MCF7, which targets MCF7 cells, specifically binds to MCF7 cells, but not other cancer cell lines. Aptamer 07-MB231, which targets MDA-MB-231 cells, binds to a series of metastatic bone and lung cancer cell lines. Aptamer 05-MB231 targets MDA-MB-231 cells, but it also binds to all of the cancer and leukemia cell lines that we examined. None of these aptamers bind to normal cell lines, such as MCF10A and HUVEC. In addition, aptamers 14A-MCF7 and 05-MB231 are internalized within the cancer cells, and aptamer 05-MB231 possesses anti-proliferative properties against most cancer cell lines that we examined. These aptamers and the generation method are broadly applicable to cancer cell imaging, biomarker discovery, cancer cell profiling, anti-cancer therapies, and drug delivery systems.
License type:
http://creativecommons.org/licenses/by/4.0/
Funding Info:
We would like to thank the Olympus Corporation (Japan), the IMB microscopy unit (Agency for Science, Technology and Research, Singapore), and the SBIC-Nikon Imaging Centre (Agency for Science, Technology and Research, Singapore) for their technical support in the confocal image scanning and analysis. This work was supported by the Institute of Bioengineering and Nanotechnology (Biomedical Research Council, Agency for Science, Technology and Research, Singapore) (to M.K. and I.H.), by a Grant-in-Aid for Scientific Research [KAKENHI 26248043] from the Ministry of Education, Culture, Sports, Science and Technology (I.H.), by grants for projects focused on developing key technologies for discovering and manufacturing drugs for next-generation treatment and diagnosis from the Ministry of Economy, Trade, and Industry (I.H.), and by the Japan Science and Technology Agency (JST) Precursory Research for Embryonic Science and Technology (PRESTO) (JPMJPR13K9 to M.K.).
Description:
ISSN:
2162-2531
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