Evidence map›Paper›PMID 36617976›Full record

ArticleNucleic acids research2023

Exploiting natural riboswitches for aptamer engineering and validation.

Michael G Mohsen, Matthew K Midy, Aparaajita Balaji, Ronald R Breaker

Abstract read
In one paragraph

Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Programming Next-Generation Synthetic Biosensors by Genetic Circuit Design.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Rapid discovery of functional RNA domains.Nucleic acids research · 2025
    Article
  11. Article
  12. gRNAde: Geometric Deep Learning for 3D RNA inverse design.bioRxiv : the preprint server for biology · 2025
    Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Michael G MohsenDepartment of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511, USA.ORCID 0000-0001-7400-9196
Matthew K MidyDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511, USA.
Aparaajita BalajiDepartment of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511, USA.
Ronald R BreakerDepartment of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511, USA.ORCID 0000-0002-2165-536X

Funding

Predoc Training at the Interface Chemistry and BiologyT32GM067543 · NIGMS · YALE UNIVERSITY · PI CRAWFORD, JASON MICHAEL · 2003 to 2022
$7.4M
Discovery and Characterization of New RiboswitchesR01GM136969 · NIGMS · YALE UNIVERSITY · PI STROBEL, SCOTT A · 2020 to 2023
$1.6M
NIGMS NIH HHS R01 GM136969NIGMS NIH HHS T32 GM067543
6 · The paper itself

Abstract

Over the past three decades, researchers have found that some engineered aptamers can be made to work well in test tubes but that these same aptamers might fail to function in cells. To help address this problem, we developed the 'Graftamer' approach, an experimental platform that exploits the architecture of a natural riboswitch to enhance in vitro aptamer selection and accelerate in vivo testing. Starting with combinatorial RNA pools that contain structural features of a guanine riboswitch aptamer interspersed with regions of random sequence, we performed multiplexed in vitro selection with a collection of small molecules. This effort yielded aptamers for quinine, guanine, and caffeine that appear to maintain structural features of the natural guanine riboswitch aptamer. Quinine and caffeine aptamers were each grafted onto a natural guanine riboswitch expression platform and reporter gene expression was monitored to determine that these aptamers function in cells. Additionally, we determined the secondary structure features and survival mechanism of a class of RNA sequences that evade the intended selection strategy, providing insight into improving this approach for future efforts. These results demonstrate that the Graftamer strategy described herein represents a convenient and straightforward approach to develop aptamers and validate their in vivo function.

Indexed as

Aptamers, NucleotideGenetic EngineeringRiboswitchCaffeineGuanineLigandsNucleic Acid ConformationQuinineAptamers, NucleotideCaffeineGuanineLigandsQuinineRiboswitch

Identifiers

PMID36617976
PMCPMC9881172

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.