Aptamer-enabled uptake of small molecule ligands
Abstract
The relative ease of isolating aptamers with high specificity for target molecules suggests that molecular recognition may be common in the folds of natural RNAs. We show here that, when expressed in cells, aptamers can increase the intracellular concentrations of their small molecule ligands. We have named these aptamers as DRAGINs (Drug Binding Aptamers for Growing Intracellular Numbers). The DRAGIN property, assessed here by the ability to enhance the toxicity of their ligands, was found for some, but not all, aminoglycoside aptamers. One aptamer protected cells against killing by its ligand. Another aptamer promoted killing as a singlemer and protected against killing as a tandemer. Based on a mathematical model, cell protection vs. killing is proposed as governed by aptamer affinity and access to the inner surface of the cell membrane, with the latter being a critical determinant. With RNA molecules proposed as the earliest functional polymers to drive the evolution of life, we suggest that RNA aptamer-like structures present in primitive cells might have selectively concentrated precursors for polymer synthesis. Riboswitches may be the evolved forms of these ancient aptamer-like “nutrient procurers”. In conclusion, aptamers with DRAGIN capability in the modern world could be applied for imaging cells, inmore »
- Authors:
-
- Ames Lab. and Iowa State Univ., Ames, IA (United States); Aptalogic Inc., Ames, IA (United States)
- Iowa State Univ., Ames, IA (United States)
- Ames Lab. and Iowa State Univ., Ames, IA (United States); Aptalogic Inc., Ames, IA (United States); Middle East Technical Univ., Ankara (Turkey)
- Ames Lab. and Iowa State Univ., Ames, IA (United States); Cornell Univ., Ithaca, NY (United States)
- Ames Lab., Ames, IA (United States)
- Ames Lab. and Iowa State Univ., Ames, IA (United States); Integrated DNA Technologies, Coralville, IA (United States)
- Ames Lab. and Iowa State Univ., Ames, IA (United States)
- Publication Date:
- Research Org.:
- Ames Laboratory (AMES), Ames, IA (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1481863
- Report Number(s):
- IS-J-9802
Journal ID: ISSN 2045-2322; PII: 33887
- Grant/Contract Number:
- AC02-07CH11358
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Scientific Reports
- Additional Journal Information:
- Journal Volume: 8; Journal Issue: 1; Journal ID: ISSN 2045-2322
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Auwardt, Supipi Liyamali, Seo, Yeon -Jung, Ilgu, Muslum, Ray, Judhajeet, Feldges, Robert R., Shubham, Shambhavi, Bendickson, Lee, Levine, Howard A., and Nilsen-Hamilton, Marit. Aptamer-enabled uptake of small molecule ligands. United States: N. p., 2018.
Web. doi:10.1038/s41598-018-33887-w.
Auwardt, Supipi Liyamali, Seo, Yeon -Jung, Ilgu, Muslum, Ray, Judhajeet, Feldges, Robert R., Shubham, Shambhavi, Bendickson, Lee, Levine, Howard A., & Nilsen-Hamilton, Marit. Aptamer-enabled uptake of small molecule ligands. United States. https://doi.org/10.1038/s41598-018-33887-w
Auwardt, Supipi Liyamali, Seo, Yeon -Jung, Ilgu, Muslum, Ray, Judhajeet, Feldges, Robert R., Shubham, Shambhavi, Bendickson, Lee, Levine, Howard A., and Nilsen-Hamilton, Marit. Wed .
"Aptamer-enabled uptake of small molecule ligands". United States. https://doi.org/10.1038/s41598-018-33887-w. https://www.osti.gov/servlets/purl/1481863.
@article{osti_1481863,
title = {Aptamer-enabled uptake of small molecule ligands},
author = {Auwardt, Supipi Liyamali and Seo, Yeon -Jung and Ilgu, Muslum and Ray, Judhajeet and Feldges, Robert R. and Shubham, Shambhavi and Bendickson, Lee and Levine, Howard A. and Nilsen-Hamilton, Marit},
abstractNote = {The relative ease of isolating aptamers with high specificity for target molecules suggests that molecular recognition may be common in the folds of natural RNAs. We show here that, when expressed in cells, aptamers can increase the intracellular concentrations of their small molecule ligands. We have named these aptamers as DRAGINs (Drug Binding Aptamers for Growing Intracellular Numbers). The DRAGIN property, assessed here by the ability to enhance the toxicity of their ligands, was found for some, but not all, aminoglycoside aptamers. One aptamer protected cells against killing by its ligand. Another aptamer promoted killing as a singlemer and protected against killing as a tandemer. Based on a mathematical model, cell protection vs. killing is proposed as governed by aptamer affinity and access to the inner surface of the cell membrane, with the latter being a critical determinant. With RNA molecules proposed as the earliest functional polymers to drive the evolution of life, we suggest that RNA aptamer-like structures present in primitive cells might have selectively concentrated precursors for polymer synthesis. Riboswitches may be the evolved forms of these ancient aptamer-like “nutrient procurers”. In conclusion, aptamers with DRAGIN capability in the modern world could be applied for imaging cells, in synthetic cell constructs, or to draw drugs into cells to make “undruggable” targets accessible to small molecule inhibitors.},
doi = {10.1038/s41598-018-33887-w},
journal = {Scientific Reports},
number = 1,
volume = 8,
place = {United States},
year = {Wed Oct 24 00:00:00 EDT 2018},
month = {Wed Oct 24 00:00:00 EDT 2018}
}
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Live-cell imaging of Pol II promoter activity to monitor gene expression with RNA IMAGEtag reporters
journal, April 2014
- Shin, Ilchung; Ray, Judhajeet; Gupta, Vinayak
- Nucleic Acids Research, Vol. 42, Issue 11
On the origins of cells: a hypothesis for the evolutionary transitions from abiotic geochemistry to chemoautotrophic prokaryotes, and from prokaryotes to nucleated cells
journal, January 2003
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journal, May 2010
- Schrum, J. P.; Zhu, T. F.; Szostak, J. W.
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Dry/Wet Cycling and the Thermodynamics and Kinetics of Prebiotic Polymer Synthesis
journal, July 2016
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Works referencing / citing this record:
Nanomaterial based aptasensors for clinical and environmental diagnostic applications
journal, January 2019
- Kaur, Harmanjit; Shorie, Munish
- Nanoscale Advances, Vol. 1, Issue 6