Evidence map›Paper›PMID 27219515›Full record

ArticleMolecular therapy. Nucleic acids2016

A New Transferrin Receptor Aptamer Inhibits New World Hemorrhagic Fever Mammarenavirus Entry.

Keith E Maier, Rohit K Jangra, Kevin R Shieh, David K Cureton, Hui Xiao, Erik L Snapp, Sean P Whelan, Kartik Chandran, Matthew Levy

Open access · goldAbstract read
PubMed Publisher
In one paragraph

Article in Molecular therapy. Nucleic acids, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
3.6field-weighted citation impact, top 7% of its field
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

33 citing papers in PubMed, 48 citations in OpenAlex.

  1. Article
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  5. Drug delivery to the central nervous system.Nature reviews. Materials · 2022
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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 at 2 institutions in 1 country.

Keith E MaierDepartment of Biochemistry, Albert Einstein College of Medicine, Bronx, New York, USA.
Rohit K JangraDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA.
Kevin R ShiehDepartment of Biochemistry, Albert Einstein College of Medicine, Bronx, New York, USA.
David K CuretonDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
Hui XiaoDepartment of Biochemistry, Albert Einstein College of Medicine, Bronx, New York, USA.
Erik L SnappDepartment of Anatomy & Structural Biology, Albert Einstein College of Medicine, Bronx, New York, USA.
Sean P WhelanDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
Kartik ChandranDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA.
Matthew LevyDepartment of Biochemistry, Albert Einstein College of Medicine, Bronx, New York, USA.
Albert Einstein College of Medicine · USHarvard University · US

Funding

RNA Processing in Non-Segmented Minus-Strand RNA VirusesR37AI059371 · NIAID · WASHINGTON UNIVERSITY · PI WHELAN, SEAN PJ · 2015 to 2024
$5.4M
Targeting CNS HIV reservoirs across the blood-brain barrierR21MH101003 · NIMH · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI LEVY, MATTHEW, PRASAD, VINAYAKA R. · 2013 to 2014
$468k
NIAID NIH HHS R37 AI059371NIMH NIH HHS R21 MH101003
6 · The paper itself

Abstract

Pathogenic New World hemorrhagic fever mammarenaviruses (NWM) utilize Glycoprotein 1 (GP1) to target the apical domain of the human transferrin receptor (hTfR) for facilitating cell entry. However, the conservation between their GP1s is low. Considering this and the slow evolutionary progression of mammals compared to viruses, therapeutic targeting of hTfR provides an attractive avenue for cross-strain inhibition and diminishing the likelihood of escape mutants. Aptamers present unique advantages for the development of inhibitors to vial entry, including ease of synthesis, lack of immunogenicity, and potentially cold-chain breaking solutions to diseases endemic to South America. Here, recognizing that in vivo competition with the natural ligand, transferrin (Tf), likely drove the evolution of GP1 to recognize the apical domain, we performed competitive in vitro selections against hTfR-expressing cells with supplemented Tf. The resultant minimized aptamer, Waz, binds the apical domain of the receptor and inhibits infection of human cells by recombinant NWM in culture (EC50 ~400 nmol/l). Aptamer multimerization further enhanced inhibition >10-fold (EC50 ~30 nmol/l). Together, our results highlight the ability to use a competitor to bias the outcome of a selection and demonstrate how avidity effects can be leveraged to enhance both aptamer binding and the potency of viral inhibition.

Identifiers

PMID27219515
OpenAlexW2402516847

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.