Evidence map›Paper›PMID 29478923›Full record

ArticleDevelopmental cell2018

Innate Immune Response and Off-Target Mis-splicing Are Common Morpholino-Induced Side Effects in Xenopus.

George E Gentsch, Thomas Spruce, Rita S Monteiro, Nick D L Owens, Stephen R Martin, James C Smith

Open access · hybridAbstract read
In one paragraph

Article in Developmental cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
3.4field-weighted citation impact, top 6% 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

27 citing papers in PubMed, 55 citations in OpenAlex.

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  5. The dishevelled associated activator of morphogenesis protein 2 (Daam2) regulates neural tube closure.Developmental dynamics : an official publication of the American Association of Anatomists · 2024
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  9. Activation of P53 pathway contributes toProceedings of the National Academy of Sciences of the United States of America · 2023
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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 1 institution in 1 country.

George E GentschThe Francis Crick Institute, Developmental Biology Laboratory, 1 Midland Road, London NW1 1AT, UK. Electronic address: george.gentsch@crick.ac.uk.
Thomas SpruceThe Francis Crick Institute, Developmental Biology Laboratory, 1 Midland Road, London NW1 1AT, UK.
Rita S MonteiroThe Francis Crick Institute, Developmental Biology Laboratory, 1 Midland Road, London NW1 1AT, UK.
Nick D L OwensThe Francis Crick Institute, Developmental Biology Laboratory, 1 Midland Road, London NW1 1AT, UK.
Stephen R MartinThe Francis Crick Institute, Structural Biology Science Technology Platform, 1 Midland Road, London NW1 1AT, UK.
James C SmithThe Francis Crick Institute, Developmental Biology Laboratory, 1 Midland Road, London NW1 1AT, UK. Electronic address: jim.smith@crick.ac.uk.
The Francis Crick Institute · GB

Funding

Cancer Research UK FC001-157Medical Research Council FC001-157Medical Research Council MC_U117597140Wellcome Trust FC001157
6 · The paper itself

Abstract

Antisense morpholino oligomers (MOs) have been indispensable tools for developmental biologists to transiently knock down (KD) genes rather than to knock them out (KO). Here we report on the implications of genetic KO versus MO-mediated KD of the mesoderm-specifying Brachyury paralogs in the frog Xenopus tropicalis. While both KO and KD embryos fail to activate the same core gene regulatory network, resulting in virtually identical morphological defects, embryos injected with control or target MOs also show a systemic GC content-dependent immune response and many off-target splicing defects. Optimization of MO dosage and increasing incubation temperatures can mitigate, but not eliminate, these MO side effects, which are consistent with the high affinity measured between MO and off-target sequence in vitro. We conclude that while MOs can be useful to profile loss-of-function phenotypes at a molecular level, careful attention must be paid to their immunogenic and off-target side effects.

Indexed as

Alternative SplicingAnimalsEmbryo, NonmammalianFemaleGene Expression Regulation, DevelopmentalGene Knockdown TechniquesMesodermMorpholinosOligonucleotides, AntisenseXenopus laevisXenopus ProteinsMorpholinosOligonucleotides, AntisenseXenopus ProteinsBrachyurydosageGC contentimmune responsemorpholinonull mutationoff-targetsplicingTALENXenopus

Identifiers

PMID29478923
PMCPMC5861998
OpenAlexW2788287704

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.