Aptamer-enabled uptake of small molecule ligands

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2018-01-01
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Liyamali Auwardt, Supipi
Seo, Yeon-Jung
Ilgu, Muslum
Ray, Judhajeet
Feldges, Robert
Shubham, Shambhavi
Bendickson, Lee
Levine, Howard
Nilsen-Hamilton, Marit
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Nilsen-Hamilton, Marit
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Ames National Laboratory

Ames National Laboratory is a government-owned, contractor-operated national laboratory of the U.S. Department of Energy (DOE), operated by and located on the campus of Iowa State University in Ames, Iowa.

For more than 70 years, the Ames National Laboratory has successfully partnered with Iowa State University, and is unique among the 17 DOE laboratories in that it is physically located on the campus of a major research university. Many of the scientists and administrators at the Laboratory also hold faculty positions at the University and the Laboratory has access to both undergraduate and graduate student talent.

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Biomedical Sciences

The Department of Biomedical Sciences aims to provide knowledge of anatomy and physiology in order to understand the mechanisms and treatment of animal diseases. Additionally, it seeks to teach the understanding of drug-action for rational drug-therapy, as well as toxicology, pharmacodynamics, and clinical drug administration.

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The Department of Biomedical Sciences was formed in 1999 as a merger of the Department of Veterinary Anatomy and the Department of Veterinary Physiology and Pharmacology.

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1999–present

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  • College of Veterinary Medicine (parent college)
  • Department of Veterinary Anatomy (predecessor, 1997)
  • Department of Veterinary Physiology and Pharmacology (predecessor, 1997)

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Mathematics
Welcome to the exciting world of mathematics at Iowa State University. From cracking codes to modeling the spread of diseases, our program offers something for everyone. With a wide range of courses and research opportunities, you will have the chance to delve deep into the world of mathematics and discover your own unique talents and interests. Whether you dream of working for a top tech company, teaching at a prestigious university, or pursuing cutting-edge research, join us and discover the limitless potential of mathematics at Iowa State University!
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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”. 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.

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This article is published as Auwardt, Supipi Liyamali, Yeon-Jung Seo, Muslum Ilgu, Judhajeet Ray, Robert R. Feldges, Shambhavi Shubham, Lee Bendickson, Howard A. Levine, and Marit Nilsen-Hamilton. "Aptamer-enabled uptake of small molecule ligands." Scientific reports 8 (2018): 15712.10.1038/s41598-018-33887-w.

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Mon Jan 01 00:00:00 UTC 2018
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