Evidence map›Paper›PMID 21106536›Full record

ArticleThe Journal of biological chemistry2011

Protection of HIV neutralizing aptamers against rectal and vaginal nucleases: implications for RNA-based therapeutics.

Michael D Moore, Jonathan Cookson, Veronica K Coventry, Brian Sproat, Lorna Rabe, Ross D Cranston, Ian McGowan, William James

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.7field-weighted citation impact, top 18% 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

17 citing papers in PubMed, 34 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Article
  6. Aptamers against pathogenic microorganisms.Critical reviews in microbiology · 2016
    Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. Article
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

8 authors at 1 institution in 1 country.

Michael D MooreSir William Dunn School of Pathology, South Parks Road, Oxford OX1 3RE, United Kingdom. kenny.moore@path.ox.ac.uk
Jonathan Cookson
Veronica K Coventry
Brian Sproat
Lorna Rabe
Ross D Cranston
Ian McGowan
William James
Magee-Womens Research Institute · US

Funding

UNIVERSITY OF PITTSBURGH CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTE: BPCAUL1RR024153 · NCRR · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI REIS, STEVEN E · 2006 to 2011
$73.9M
Aptamer Microbicide Development Program (MDP)U01AI066734 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MCGOWAN, IAN MICHAEL · 2005 to 2009
$3.2M
Medical Research Council G0401610NCRR NIH HHS 1 UL1 RR024153NCRR NIH HHS UL1 RR024153NIAID NIH HHS U01 AI066734
6 · The paper itself

Abstract

RNA-based drugs are an emerging class of therapeutics. They have the potential to regulate proteins, chromatin, as well as bind to specific proteins of interest in the form of aptamers. These aptamers are protected from nuclease attack by chemical modifications that enhance their stability for in vivo usage. However, nucleases are ubiquitous, and as we have yet to characterize the entire human microbiome it is likely that many nucleases are yet to be identified. Any novel, unusual enzymes present in vivo might reduce the efficacy of RNA-based therapeutics, even when they are chemically modified. We have previously identified an RNA-based aptamer capable of neutralizing a broad spectrum of clinical HIV-1 isolates and are developing it as a vaginal and rectal microbicide candidate. As a first step we addressed aptamer stability in the milieu of proteins present in these environments. Here we uncover a number of different nucleases that are able to rapidly degrade 2'-F-modified RNA. We demonstrate that the aptamer can be protected from the nuclease(s) present in the vaginal setting, without affecting its antiviral activity, by replacement of key positions with 2'-O-Me-modified nucleotides. Finally, we show that the aptamer can be protected from all nucleases present in both vaginal and rectal compartments using Zn(2+) cations. In conclusion we have derived a stable, antiviral RNA-based aptamer that could form the basis of a pre-exposure microbicide or be a valuable addition to the current tenofovir-based microbicide candidate undergoing clinical trials.

Indexed as

HIV-1Antiviral AgentsAptamers, NucleotideDrug Evaluation, PreclinicalFemaleHIV InfectionsHumansMaleRectumRibonucleasesVaginaAntiviral AgentsAptamers, NucleotideRibonucleases

Identifiers

PMID21106536
PMCPMC3024747
OpenAlexW1987991458

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.