Evidence map›Paper›PMID 22446693›Full record

ArticleNature biotechnology2012

Inhibition of natural antisense transcripts in vivo results in gene-specific transcriptional upregulation.

Farzaneh Modarresi, Mohammad Ali Faghihi, Miguel A Lopez-Toledano, Roya Pedram Fatemi, Marco Magistri, Shaun P Brothers, Marcel P van der Brug, Claes Wahlestedt

Open access · greenAbstract read
In one paragraph

Article in Nature biotechnology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 374 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
374citing papers in PubMed, 2 pooled it
22.6field-weighted citation impact, top 1% 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

374 citing papers in PubMed, 2 syntheses or guidelines pooled it, 672 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Review
  5. Review
  6. Article
  7. Are RNA Therapies a Solid Foundation or a Frontier Yet to Be Conquered?International journal of molecular sciences · 2026
    Review
  8. The Versatile Applications of Antisense Oligonucleotides in Modern Medicine.International journal of molecular sciences · 2026
    Review
  9. Article
  10. Review
  11. Review
  12. Article
  13. Review
  14. Targeted BDNF upregulation via upstream open reading frame disruption.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Review
  20. Article

314 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Farzaneh ModarresiDepartment of Psychiatry and Behavioral Sciences and Center for Therapeutic Innovation, John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Mohammad Ali Faghihi
Miguel A Lopez-Toledano
Roya Pedram Fatemi
Marco Magistri
Shaun P Brothers
Marcel P van der Brug
Claes Wahlestedt
University of Miami · USFlorida Atlantic University · US

Funding

Regulatory RNAs as mediators and biomarkers in Alzheimer's DiseaseR01NS063974 · NINDS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI WAHLESTEDT, CLAES ROBERT · 2009 to 2012
$1.6M
Noncoding RNAs as epigenomic modulators in Alzheimer's DiseaseRC2AG036596 · NIA · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI WAHLESTEDT, CLAES ROBERT · 2009 to 2010
$915k
NIA NIH HHS 5RC2AG036596NIA NIH HHS RC2 AG036596NINDS NIH HHS 5R01NS063974NINDS NIH HHS R01 NS063974
6 · The paper itself

Abstract

The ability to specifically upregulate genes in vivo holds great therapeutic promise. Here we show that inhibition or degradation of natural antisense transcripts (NATs) by single-stranded oligonucleotides or siRNAs can transiently and reversibly upregulate locus-specific gene expression. Brain-derived neurotrophic factor (BDNF) is normally repressed by a conserved noncoding antisense RNA transcript, BDNF-AS. Inhibition of this transcript upregulates BDNF mRNA by two- to sevenfold, alters chromatin marks at the BDNF locus, leads to increased protein levels and induces neuronal outgrowth and differentiation both in vitro and in vivo. We also show that inhibition of NATs leads to increases in glial-derived neurotrophic factor (GDNF) and ephrin receptor B2 (EPHB2) mRNA. Our data suggest that pharmacological approaches targeting NATs can confer locus-specific gene upregulation effects.

Indexed as

Up-RegulationAnimalsCell LineChromatinExonsGene Expression ProfilingGenomicsGlial Cell Line-Derived Neurotrophic FactorHEK293 CellsHumansMiceModels, GeneticOligonucleotides, AntisenseReceptor, EphB2RNA, MessengerRNA, Small InterferingChromatinGlial Cell Line-Derived Neurotrophic FactorOligonucleotides, AntisenseReceptor, EphB2RNA, MessengerRNA, Small Interfering

Identifiers

PMID22446693
PMCPMC4144683
OpenAlexW2154942988

What OpenQuestion holds

Textmetadata
LicenceTDM
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.