Evidence map›Paper›PMID 34927791›Full record

ArticleEMBO reports2022

Unexpected gene activation following CRISPR-Cas9-mediated genome editing.

Anna G Manjón, Simon Linder, Hans Teunissen, Anoek Friskes, Wilbert Zwart, Elzo de Wit, René H Medema

Open access · hybridAbstract read
In one paragraph

Article in EMBO reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.6field-weighted citation impact, top 35% 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

9 citing papers in PubMed, 10 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

7 authors at 1 institution in 1 country.

Anna G ManjónOncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands.ORCID 0000-0003-3255-5062
Simon LinderOncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Hans TeunissenOncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Anoek FriskesOncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands.ORCID 0000-0002-9845-3715
Wilbert ZwartOncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Elzo de WitOncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands.ORCID 0000-0003-2883-1415
René H MedemaOncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands.ORCID 0000-0002-6754-0381
The Netherlands Cancer Institute · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The discovery of the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and its development as a genome editing tool has revolutionized the field of molecular biology. In the DNA damage field, CRISPR has brought an alternative to induce endogenous double-strand breaks (DSBs) at desired genomic locations and study the DNA damage response and its consequences. Many systems for sgRNA delivery have been reported in order to efficiently generate this DSB, including lentiviral vectors. However, some of the consequences of these systems are not yet well understood. Here, we report that lentiviral-based sgRNA vectors can integrate into the endogenous genomic target location, leading to undesired activation of the target gene. By generating a DSB in the regulatory region of the ABCB1 gene using a lentiviral sgRNA vector, we can induce the formation of Taxol-resistant colonies. We show that these colonies upregulate ABCB1 via integration of the EEF1A1 and the U6 promoters from the sgRNA vector. We believe that this is an unreported CRISPR/Cas9 on-target effect that researchers need to be aware of when using lentiviral vectors for genome editing.

Indexed as

CRISPR-Cas SystemsGene EditingTranscriptional ActivationCRISPR-Cas9drug resistancegene activationlentiviral integrationon-target effects

Identifiers

PMID34927791
PMCPMC8811649
OpenAlexW4200096333

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.