Evidence map›Paper›PMID 17536839›Full record

ArticleBiochemistry2007

Inhibiting gene expression with locked nucleic acids (LNAs) that target chromosomal DNA.

Randall L Beane, Rosalyn Ram, Sylvie Gabillet, Khalil Arar, Brett P Monia, David R Corey

Open access · greenAbstract read
In one paragraph

Article in Biochemistry, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.9field-weighted citation impact, top 15% 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, 42 citations in OpenAlex.

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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

6 authors at 2 institutions in 2 countries.

Randall L BeaneDepartment of Pharmacology, University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park Road, Dallas, Texas 75390-9041, USA.
Rosalyn Ram
Sylvie Gabillet
Khalil Arar
Brett P Monia
David R Corey
Genopole (France) · FRSouthwestern Medical Center · US

Funding

Recognition of Chromosomal DNA by Peptide Nucleic AcidsR01GM073042 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI COREY, DAVID R · 2005 to 2016
$3.5M
CONTROLLING GENE EXPRESSION WITH PEPTIDE NUCLEIC ACIDSR01GM060642 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI COREY, DAVID R. · 2000 to 2007
$2.2M
NIGMS NIH HHS R01 GM060642NIGMS NIH HHS R01 GM073042PHS HHS 60642PHS HHS 73042
6 · The paper itself

Abstract

Oligonucleotides containing locked nucleic acid bases (LNAs) have increased affinity for complementary DNA sequences. We hypothesized that enhanced affinity might allow LNAs to recognize chromosomal DNA inside human cells and inhibit gene expression. To test this hypothesis, we synthesized antigene LNAs (agLNAs) complementary to sequences within the promoters of progesterone receptor (PR) and androgen receptor (AR). We observed inhibition of AR and PR expression by agLNAs but not by analogous oligomers containing 2'-methoxyethyl bases or noncomplementary LNAs. Inhibition was dose dependent and exhibited IC50 values of <10 nM. Efficient inhibition depended on the length of the agLNA, the location of LNA bases, the number of LNA substitutions, and the location of the target sequence within the targeted promoter. LNAs targeting sequences at or near transcription start sites yielded better inhibition than LNAs targeting transcription factor binding sites or an inverted repeat. These results demonstrate that agLNAs can recognize chromosomal target sequences and efficiently block gene expression. agLNAs could be used for gene silencing, as cellular probes for chromosome structure, and therapeutic applications.

Indexed as

Gene TargetingAndrogen Receptor AntagonistsBase SequenceBreast NeoplasmsCell Line, TumorChromosomesDNADose-Response Relationship, DrugFemaleGene Expression Regulation, NeoplasticHumansInhibitory Concentration 50Molecular Sequence DataMolecular StructureNucleic AcidsOligonucleotidesAndrogen Receptor AntagonistsDNANucleic AcidsOligonucleotidesReceptors, AndrogenReceptors, Progesterone

Identifiers

PMID17536839
PMCPMC2527755
OpenAlexW2062253159

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.