Aptamer-enabled uptake of small molecule ligands

Auwardt, Supipi Liyamali; Seo, Yeon -Jung; Ilgu, Muslum; Ray, Judhajeet; Feldges, Robert R.; Shubham, Shambhavi; Bendickson, Lee; Levine, Howard A.; Nilsen-Hamilton, Marit

doi:10.1038/s41598-018-33887-w

Aptamer-enabled uptake of small molecule ligands

Journal Article · Wed Oct 24 00:00:00 EDT 2018 · Scientific Reports

DOI:https://doi.org/10.1038/s41598-018-33887-w· OSTI ID:1481863

Auwardt, Supipi Liyamali ^[1]; Seo, Yeon -Jung ^[2]; Ilgu, Muslum ^[3]; Ray, Judhajeet ^[4]; Feldges, Robert R. ^[5]; Shubham, Shambhavi ^[6]; Bendickson, Lee ^[7]; Levine, Howard A. ^[2]; Nilsen-Hamilton, Marit ^[1]

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)

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.

View Accepted Manuscript (DOE)

Research Organization:: Ames Laboratory (AMES), Ames, IA (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC02-07CH11358

OSTI ID:: 1481863

Report Number(s):: IS-J--9802; PII: 33887

Journal Information:: Scientific Reports, Journal Name: Scientific Reports Journal Issue: 1 Vol. 8; ISSN 2045-2322

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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Nanomaterial based aptasensors for clinical and environmental diagnostic applications Kaur, Harmanjit; Shorie, Munish Nanoscale Advances, Vol. 1, Issue 6 https://doi.org/10.1039/c9na00153k	journal	January 2019

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