In vitro selection of DNA aptamers against human osteosarcoma

被引:0
作者
Khaliunsarnai Tsogtbaatar
Diana A. Sousa
Debora Ferreira
Atakan Tevlek
Halil Murat Aydın
Eda Çelik
Ligia Rodrigues
机构
[1] Hacettepe University,Institute of Science
[2] University of Minho,CEB
[3] Hacettepe University, Centre of Biological Engineering
[4] Hacettepe University,Centre for Bioengineering
来源
Investigational New Drugs | 2022年 / 40卷
关键词
Aptamers; Osteosarcoma; Cell-SELEX; MG-63 cell line; Early cancer diagnosis; Therapeutics;
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摘要
Background. Osteosarcoma is a highly malignant bone tumor, most frequently occurring in the rapid bone growth phase. Effective treatment of this disease is hindered by the lack of specific probes for early diagnosis and the fast cancer widespread. Methods. To find such probes, the cell-Systematic Evolution of Ligands by EXponential enrichment (cell-SELEX) methodology was implemented against the human osteosarcoma MG-63 cell line towards the selection of new specific aptamers. After 10 rounds of selection, the aptamer DNA pool was Sanger sequenced and the sequences were subjected to a bioinformatic analysis that included sequence alignment, phylogenetic relationship, and secondary structure prediction. Results. A DNA aptamer (OS-7.9), with a dissociation constant (Kd) value in the nanomolar range (12.8 ± 0.9 nM), revealed high affinity against the target cells at the physiological temperature. Furthermore, the selected aptamer also recognized lung carcinoma and colon colorectal adenocarcinoma cell lines, which are reported as common metastasis sites of osteosarcoma. Conclusions. These results suggest that OS-7.9 could recognize a common protein expressed in these cancer cells, possibly becoming a potential molecular probe for early diagnosis and targeted therapies for metastatic disease. Moreover, to the best of our knowledge, this was the first attempt to generate a DNA aptamer (OS-7.9 aptamer) against the MG-63-cell line by cell-SELEX.
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页码:172 / 181
页数:9
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  • [1] Taran S(2017)Pediatric osteosarcoma: An updated review Indian J Med Paediatr Oncol 38 33-153
  • [2] Taran R(2002)Osteogenic Sarcoma Presenting with Lung Metastasis Oncologist 7 144-77
  • [3] Malipatil N(2013)The Current and Future Therapies for Human Osteosarcoma Curr Cancer Ther Rev 9 55-735
  • [4] Staddon AP(2014)Translational biology of osteosarcoma Nat Rev Cancer 14 722-274
  • [5] Lackman R(2016)Advances in osteosarcoma stem cell research and opportunities for novel therapeutic targets Cancer Lett 370 268-202
  • [6] Robinson K(2017)Aptamers as targeted therapeutics: Current potential and challenges Nat Rev Drug Discov 16 181-403
  • [7] Lamplot J(2007)SELEX—A (r)evolutionary method to generate high-affinity nucleic acid ligands Biomol Eng 24 381-2254
  • [8] Denduluri S(2015)Characterisation of aptamer-target interactions by branched selection and high-throughput sequencing of SELEX pools Nucleic Acids Res 43 2235-87
  • [9] Qin J(2015)Aptamer Nanomedicine for Cancer Therapeutics: Barriers and Potential for Translation ACS Nano 9 75-1185
  • [10] Kansara M(2011)Strategies for the discovery of therapeutic aptamers Expert Opin Drug Discov 6 1169-18157