Evidence map›Paper›PMID 34994962›Full record

ArticleMolecular diagnosis & therapy2022

Reduction of Off-Target Effects of Gapmer Antisense Oligonucleotides by Oligonucleotide Extension.

Hidenori Yasuhara, Tokuyuki Yoshida, Kiyomi Sasaki, Satoshi Obika, Takao Inoue

Open access · hybridAbstract read
In one paragraph

Article in Molecular diagnosis & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
4.3field-weighted citation impact, top 4% 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

32 citing papers in PubMed, 55 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

5 authors at 3 institutions in 1 country.

Hidenori Yasuhara *Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan.
Tokuyuki Yoshida *Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan.
Kiyomi SasakiDivision of Molecular Target and Gene Therapy Products, National Institute of Health Sciences, Kawasaki, Kanagawa, Japan.
Satoshi ObikaGraduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan. obika@phs.osaka-u.ac.jp.
Takao InoueGraduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan. takao@nihs.go.jp.ORCID 0000-0002-6507-9480
National Institute of Health Sciences · JPOsaka University of Pharmaceutical Sciences · JPThe University of Osaka · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimAntisense oligonucleotide (ASO) has the potential to induce off-target effects by inadvertent binding of ASOs to unintended RNAs that have a sequence similar to the target RNA. In the present study, we focused on the association between oligonucleotide length and off-target effects. Oligonucleotide extension is assumed to have bilateral effects on hybridization-dependent changes in gene expression, i.e., one is the decrease of off-target effects based on the reduced number of off-target candidate genes with perfect matches, and the other is the increase of off-target effects based on the increased binding affinity between the ASO and the complementary RNAs that leads to better tolerability for mismatches.

methodsTo determine the effects of oligonucleotide extension of gapmer ASOs on off-target effects, an extensive microarray analysis was performed using human cells treated with a 14-mer gapmer ASO and the extended 18-mer derivatives with the same core 14-mer region. RESULTS AND DISCUSSION: Our data indicated that change in gene expression in the cells treated with 18-mer ASOs was significantly smaller than those with a 14-mer ASO, showing the decrease of off-target effects by oligonucleotide extension.

Indexed as

OligonucleotidesOligonucleotides, AntisenseHumansRNAOligonucleotidesOligonucleotides, AntisenseRNA

Identifiers

PMID34994962
PMCPMC8766371
OpenAlexW4206206618

What OpenQuestion holds

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LicenceCC BY-NC
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.