Evidence map›Paper›PMID 22962591›Full record

ArticlePloS one2012

Rapid identification of cell-specific, internalizing RNA aptamers with bioinformatics analyses of a cell-based aptamer selection.

William H Thiel, Thomas Bair, Andrew S Peek, Xiuying Liu, Justin Dassie, Katie R Stockdale, Mark A Behlke, Francis J Miller, Paloma H Giangrande

Abstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.

0numbers the graph read from it
0cells of the map it votes in
77citing 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

77 citing papers in PubMed.

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  12. Evolution of Cell-Type-Specific RNA Aptamers via Live Cell-Based SELEX.Methods in molecular biology (Clifton, N.J.) · 2023
    Article
  13. Review
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17 more citing papers are in PubMed but not listed here.

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

9 authors.

William H ThielDepartment of Internal Medicine, University of Iowa, Iowa City, Iowa, United States of America.
Thomas Bair
Andrew S Peek
Xiuying Liu
Justin Dassie
Katie R Stockdale
Mark A Behlke
Francis J Miller
Paloma H Giangrande

Funding

INTERDISCIPLINARY CARDIOVASCULAR RESEARCH FELLOWSHIPT32HL007121 · NHLBI · UNIVERSITY OF IOWA · PI LONDON, BARRY · 1985 to 2020
$15.1M
PROGRAM IN HEMOSTASIS AND THROMBOSIS FOR ACADEMICT32HL007344 · NHLBI · UNIVERSITY OF IOWA · PI Anil Kumar Chauhan, Steven R Lentz · 1985 to 2026
$6.5M
Aptamer-siRNA Chimeras Targeting HER2-Positive Breast CancersR01CA138503 · NCI · UNIVERSITY OF IOWA · PI GIANGRANDE, PALOMA HOBAN · 2009 to 2013
$1.5M
Novel Chimeric RNA Aptamer Technology to Treat Head and Neck CancerR21DE019953 · NIDCR · UNIVERSITY OF IOWA · PI GIANGRANDE, PALOMA HOBAN, KLINGELHUTZ, ALOYSIUS JOHN · 2009 to 2010
$410k
American Heart Association-American Stroke Association 11POST7620018NCI NIH HHS 1R01 CA138503-01NCI NIH HHS R01 CA138503NHLBI NIH HHS 2 T32 HL007121-36NHLBI NIH HHS T32 HL007121NHLBI NIH HHS T32 HL007344NIDCR NIH HHS 1R21DE019953-01NIDCR NIH HHS R21 DE019953
6 · The paper itself

Abstract

backgroundThe broad applicability of RNA aptamers as cell-specific delivery tools for therapeutic reagents depends on the ability to identify aptamer sequences that selectively access the cytoplasm of distinct cell types. Towards this end, we have developed a novel approach that combines a cell-based selection method (cell-internalization SELEX) with high-throughput sequencing (HTS) and bioinformatics analyses to rapidly identify cell-specific, internalization-competent RNA aptamers. METHODOLOGY/PRINCIPAL

findingsWe demonstrate the utility of this approach by enriching for RNA aptamers capable of selective internalization into vascular smooth muscle cells (VSMCs). Several rounds of positive (VSMCs) and negative (endothelial cells; ECs) selection were performed to enrich for aptamer sequences that preferentially internalize into VSMCs. To identify candidate RNA aptamer sequences, HTS data from each round of selection were analyzed using bioinformatics methods: (1) metrics of selection enrichment; and (2) pairwise comparisons of sequence and structural similarity, termed edit and tree distance, respectively. Correlation analyses of experimentally validated aptamers or rounds revealed that the best cell-specific, internalizing aptamers are enriched as a result of the negative selection step performed against ECs. CONCLUSIONS AND SIGNIFICANCE: We describe a novel approach that combines cell-internalization SELEX with HTS and bioinformatics analysis to identify cell-specific, cell-internalizing RNA aptamers. Our data highlight the importance of performing a pre-clear step against a non-target cell in order to select for cell-specific aptamers. We expect the extended use of this approach to enable the identification of aptamers to a multitude of different cell types, thereby facilitating the broad development of targeted cell therapies.

Indexed as

Drug Delivery SystemsSELEX Aptamer TechniqueAptamers, NucleotideBiological TransportComputational BiologyEndothelial CellsGene LibraryHigh-Throughput Nucleotide SequencingHumansMuscle, Smooth, VascularMyocytes, Smooth MuscleRNAAptamers, NucleotideRNA

Identifiers

PMID22962591
PMCPMC3433472

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.