Evidence map›Paper›PMID 29311693›Full record

ArticleScientific reports2018

Combined shRNA over CRISPR/cas9 as a methodology to detect off-target effects and a potential compensatory mechanism.

Liat Peretz, Elazar Besser, Renana Hajbi, Natania Casden, Dan Ziv, Nechama Kronenberg, Liat Ben Gigi, Sahar Sweetat, Saleh Khawaled, Rami Aqeilan and 1 more

Abstract read
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
–field-weighted citation impact
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

25 citing papers in PubMed.

  1. Review
  2. Synthetic nucleic acids in a post-agent biosecurity Era.Frontiers in bioengineering and biotechnology · 2026
    Article
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  4. Review
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  6. Article
  7. Delivery Strategies of siRNA Therapeutics for Hair Loss Therapy.International journal of molecular sciences · 2024
    Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. 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

11 authors.

Liat PeretzDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research, Faculty of Medicine, The Hebrew University, Ein Kerem, P.O. Box 12271, Jerusalem, 91120, Israel.
Elazar BesserDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research, Faculty of Medicine, The Hebrew University, Ein Kerem, P.O. Box 12271, Jerusalem, 91120, Israel.
Renana HajbiDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research, Faculty of Medicine, The Hebrew University, Ein Kerem, P.O. Box 12271, Jerusalem, 91120, Israel.
Natania CasdenDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research, Faculty of Medicine, The Hebrew University, Ein Kerem, P.O. Box 12271, Jerusalem, 91120, Israel.
Dan ZivDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research, Faculty of Medicine, The Hebrew University, Ein Kerem, P.O. Box 12271, Jerusalem, 91120, Israel.
Nechama KronenbergDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research, Faculty of Medicine, The Hebrew University, Ein Kerem, P.O. Box 12271, Jerusalem, 91120, Israel.
Liat Ben GigiDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research, Faculty of Medicine, The Hebrew University, Ein Kerem, P.O. Box 12271, Jerusalem, 91120, Israel.
Sahar SweetatDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research, Faculty of Medicine, The Hebrew University, Ein Kerem, P.O. Box 12271, Jerusalem, 91120, Israel.
Saleh KhawaledLautenberg Center for Immunology and Cancer Research, The Institute for Medical Research, Faculty of Medicine, The Hebrew University, Ein Kerem, P.O. Box 12271, Jerusalem, 91120, Israel.
Rami AqeilanLautenberg Center for Immunology and Cancer Research, The Institute for Medical Research, Faculty of Medicine, The Hebrew University, Ein Kerem, P.O. Box 12271, Jerusalem, 91120, Israel.
Oded BeharDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research, Faculty of Medicine, The Hebrew University, Ein Kerem, P.O. Box 12271, Jerusalem, 91120, Israel. odedb@ekmd.huji.ac.il.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Inhibition of genes is a powerful approach to study their function. While RNA interference is a widely used method to achieve this goal, mounting evidence indicates that such an approach is prone to off-target effects. An alternative approach to gene function inhibition is genetic mutation, such as the CRISPR/cas9 method. A recent report, however, demonstrated that genetic mutation and inhibition of gene expression do not always give corresponding results. This can be explained by off-target effects, but it was recently shown, at least in one case, that these differences are the result of a compensatory mechanism induced only by genetic mutation. We present here a combination of RNA inhibition and CRISPR/cas9 methods to identify possible off targets as well as potential compensatory effects. This approach is demonstrated by testing a possible role for Sema4B in glioma biology, in which our results implicate Sema4B as having a critical function. In stark contrast, by using shRNA over CRISPR/cas9 combined methodology, we clearly demonstrate that the Sema4B targeted shRNA effects on cell proliferation is the result of off-target effects. Nevertheless, it also revealed that certain splice variants of Sema4B are important for the ability of glioma cells to grow as individual clones.

Indexed as

CRISPR-Cas SystemsAnimalsCell DeathCell Line, TumorDisease Models, AnimalGene Knockdown TechniquesGliomaHeterograftsHumansMiceRNA InterferenceRNA, Small InterferingSemaphorinsRNA, Small Interferingsemaphorin 4B, humanSemaphorins

Identifiers

PMID29311693
PMCPMC5758708

What OpenQuestion holds

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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.