Evidence map›Paper›PMID 35314779›Full record

ArticleGene therapy2022

Exon skipping induced by CRISPR-directed gene editing regulates the response to chemotherapy in non-small cell lung carcinoma cells.

Kelly Banas, Shirin Modarai, Natalia Rivera-Torres, Byung-Chun Yoo, Pawel A Bialk, Connor Barrett, Mona Batish, Eric B Kmiec

Open access · hybridAbstract read
In one paragraph

Article in Gene therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.4field-weighted citation impact, top 20% 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

13 citing papers in PubMed, 17 citations in OpenAlex.

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  13. Applications and advancements of CRISPR-Cas in the treatment of lung cancer.Frontiers in cell and developmental biology · 2023
    Review
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

8 authors at 2 institutions in 1 country.

Kelly BanasGene Editing Institute, ChristianaCare, Newark, DE, USA.
Shirin ModaraiGene Editing Institute, ChristianaCare, Newark, DE, USA.
Natalia Rivera-TorresGene Editing Institute, ChristianaCare, Newark, DE, USA.
Byung-Chun YooGene Editing Institute, ChristianaCare, Newark, DE, USA.
Pawel A BialkGene Editing Institute, ChristianaCare, Newark, DE, USA.
Connor BarrettDepartment of Medical and Molecular Sciences, University of Delaware, Newark, DE, USA.
Mona BatishDepartment of Medical and Molecular Sciences, University of Delaware, Newark, DE, USA.ORCID http://orcid.org/0000-0001-9039-6149
Eric B KmiecGene Editing Institute, ChristianaCare, Newark, DE, USA. Eric.B.Kmiec@christianacare.org.ORCID http://orcid.org/0000-0003-0588-6130
University of Delaware · USChristiana Care Health System · US

Funding

Predictive Modeling & Optimal Control Framework for Model-Based Epidemic Response in DelawareP20GM103446 · NIGMS · UNIVERSITY OF DELAWARE · PI MELINDA K DUNCAN · 2012 to 2026
$67.2M
The eye as a window into sickle cell disease morbidityP20GM109021 · NIGMS · NEMOURS CHILDREN'S HOSPITAL, DELAWARE · PI HILDENBRAND, AIMEE K · 2014 to 2025
$20.7M
NIGMS NIH HHS P20 GM103446NIGMS NIH HHS P20 GM109021
6 · The paper itself

Abstract

We have been developing CRISPR-directed gene editing as an augmentative therapy for the treatment of non-small cell lung carcinoma (NSCLC) by genetic disruption of Nuclear Factor Erythroid 2-Related Factor 2 (NRF2). NRF2 promotes tumor cell survival in response to therapeutic intervention and thus its disablement should restore or enhance effective drug action. Here, we report how NRF2 disruption leads to collateral damage in the form of CRISPR-mediated exon skipping. Heterogeneous populations of transcripts and truncated proteins produce a variable response to chemotherapy, dependent on which functional domain is missing. We identify and characterize predicted and unpredicted transcript populations and discover that several types of transcripts arise through exon skipping; wherein one or two NRF2 exons are missing. In one specific case, the presence or absence of a single nucleotide determines whether an exon is skipped or not by reorganizing Exonic Splicing Enhancers (ESEs). We isolate and characterize the diversity of clones induced by CRISPR activity in a NSCLC tumor cell population, a critical and often overlooked genetic byproduct of this exciting technology. Finally, gRNAs must be designed with care to avoid altering gene expression patterns that can account for variable responses to solid tumor therapy.

Indexed as

Carcinoma, Non-Small-Cell LungLung NeoplasmsClustered Regularly Interspaced Short Palindromic RepeatsExonsGene EditingHumansNF-E2-Related Factor 2NF-E2-Related Factor 2

Identifiers

PMID35314779
PMCPMC9203268
OpenAlexW4220947704

What OpenQuestion holds

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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.