4.8 Article

Engineering G-quadruplex aptamer to modulate its binding specificity

期刊

NATIONAL SCIENCE REVIEW
卷 8, 期 4, 页码 -

出版社

OXFORD UNIV PRESS
DOI: 10.1093/nsr/nwaa202

关键词

G-quadruplex; aptamer; i-motif; binding specificity; cell microenvironment

资金

  1. National Institutes of Health [GM079359, CA133086]
  2. Natural Science Foundation of China [21505032, 21325520, 1327009]

向作者/读者索取更多资源

The use of aptamers in bio analytical and biomedical applications exploits their ability to recognize cell surface protein receptors, making them valuable tools in targeted therapeutics. A strategy of constructing structure-switching aptamers has been developed, enhancing target cell recognition by engineering aptamers with DNA intercalated motifs responsive to the microenvironment. Structure-switching sensitivity can be tuned by manipulating i-motif sequences, but estimating this sensitivity is challenging.
The use of aptamers in bio analytical and biomedical applications exploits their ability to recognize cell surface protein receptors. Targeted therapeutics and theranostics come to mind in this regard. However, protein receptors occur on both cancer and normal cells; as such, aptamers are now taxed with identifying high vs. low levels of protein expression. Inspired by the flexible template mechanism and elegant control of natural nucleic acid-based structures, we report an allosteric regulation strategy for constructing a structure-switching aptamer for enhanced target cell recognition by engineering aptamers with DNA intercalated motifs (i-motifs) responsive to the microenvironment, such as pH. Structure-switching sensitivity can be readily tuned by manipulating i-motif sequences. However, structure-switching sensitivity is difficult to estimate, making it equally difficult to effectively screen modified aptamers with the desired sensitivity. To address this problem, we selected a fluorescent probe capable of detecting G-quadruplex in complicated biological media.

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