Evidence map›Paper›PMID 25689224›Full record

ArticleMolecular therapy. Nucleic acids2015

High-affinity RNA Aptamers Against the HIV-1 Protease Inhibit Both In Vitro Protease Activity and Late Events of Viral Replication.

Sonald Duclair, Archana Gautam, Andrew Ellington, Vinayaka R Prasad

Open access · goldAbstract read
In one paragraph

Article in Molecular therapy. Nucleic acids, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 10% 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

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.

  1. Aptamers used for biosensors and targeted therapy.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2020
    Pooled it
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. Aptamers for Anti-Viral Therapeutics and Diagnostics.International journal of molecular sciences · 2021
    Review
  10. Review
  11. Review
  12. Development of a novel, high-affinity ssDNA trypsin inhibitor.Journal of enzyme inhibition and medicinal chemistry · 2019
    Article
  13. Article
  14. Review
  15. Article
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  17. Review
  18. Article
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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

4 authors at 2 institutions in 1 country.

Sonald DuclairDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA.
Archana GautamDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA.
Andrew EllingtonDepartment of Chemistry and Biochemistry, University of Texas at Austin, Austin, Texas, USA.
Vinayaka R PrasadDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA.
Albert Einstein College of Medicine · USThe University of Texas at Austin · US

Funding

Training in HIV/AIDS Pathogenesis; Basic and Translational ResearchT32AI007501 · NIAID · YESHIVA UNIVERSITY · PI PRASAD, VINAYAKA R. · 1995 to 2024
$6.6M
The role of viral and cellular proteins in early events of HIV-1 replicationR37AI030861 · NIAID · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI PRASAD, VINAYAKA R. · 2007 to 2016
$4.4M
High throughput selection and character. of aptamersP01AI061797 · NIAID · ALBERT EINSTEIN COL OF MED YESHIVA UNIV · PI LEVY, MATTHEW · 2004 to 2007
$3.6M
RNA Aptamers Targeted to HIV-1 PR, Vif and Nef ProteinsF31GM078730 · NIGMS · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI DUCLAIR, SONALD · 2006 to 2008
$165k
NIAID NIH HHS P01 AI061797NIAID NIH HHS R37 AI030861NIAID NIH HHS T32 AI007501NIGMS NIH HHS F31 GM078730
6 · The paper itself

Abstract

HIV-1 aspartyl protease (PR) plays a key role in virion morphogenesis, underscoring the effectiveness of protease inhibitors (PI). Despite their utility, side effects and drug-resistance remains a problem. We report the development of RNA aptamers as inhibitors of HIV-1 PR for potential use in anti-HIV gene therapy. Employing Systematic Evolution of Ligands by Exponential Enrichment (SELEX), we isolated four unique families of anti-HIV-1 PR RNA aptamers displaying moderate binding affinities (Kd = 92-140 nmol/l) and anti-PR inhibitory activity (Kis = 138-647 nmol/l). Second-generation RNA aptamers selected from partially randomized pools based on two of the aptamer sequences displayed striking enhancements in binding (Kds = 2-22 nmol/l) and inhibition (Kis = 31-49 nmol/l). The aptamers were specific in that they did not bind either the related HIV-2 protease, or the cellular aspartyl protease, Cathepsin D. Site-directed mutagenesis of a second-generation aptamer to probe the predicted secondary structure indicated that the stem-loops SL2 and SL3 and the stem P1 were essential for binding and that only the 3'-most 17 nucleotides were dispensable. Anti-PR aptamers inhibited HIV replication in vitro and the degree of inhibition was higher for second-generation aptamers with greater affinity and the inhibition was abrogated for a nonbinding aptamer variant.

Identifiers

PMID25689224
PMCPMC4345311
OpenAlexW2040273699

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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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.