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Cited by 399

The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.

An Inducible Lentiviral Guide RNA Platform Enables the Identification of Tumor-Essential Genes and Tumor-Promoting Mutations In Vivo

Open access
Aubrey, Brandon J., Kelly, Gemma L., Kueh, Andrew J., Brennan, Margs S., O’Connor, Liam, Milla, Liz, Wilcox, Stephen, Tai, Lin, Strasser, Andreas, Herold, Marco J.·2015·Cell Reports

Abstract

The CRISPR/Cas9 technology enables the introduction of genomic alterations into almost any organism; however, systems for efficient and inducible gene modification have been lacking, especially for deletion of essential genes. Here, we describe a drug-inducible small guide RNA (sgRNA) vector system allowing for ubiquitous and efficient gene deletion in murine and human cells. This system mediates the efficient, temporally controlled deletion of MCL-1, both in vitro and in vivo, in human Burkitt lymphoma cell lines that require this anti-apoptotic BCL-2 protein for sustained survival and growth. Unexpectedly, repeated induction of the same sgRNA generated similar inactivating mutations in the human Mcl-1 gene due to low mutation variability exerted by the accompanying non-homologous end-joining (NHEJ) process. Finally, we were able to generate hematopoietic cell compartment-restricted Trp53-knockout mice, leading to the identification of cancer-promoting mutants of this critical tumor suppressor.

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Registry

Crossref · 10.1016/j.celrep.2015.02.002

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Metadata

Authors
Aubrey, B. J., Kelly, G. L., Kueh, A. J., Brennan, M. S., O’Connor, L., Milla, L., Wilcox, S., Tai, L., Strasser, A., & Herold, M. J.
Venue
Cell Reports
Publisher
Elsevier BV
Published
2015-03
Volume
10
Issue
8
Pages
1422-1432
ISSN
2211-1247 (ISSN-L)
OpenAlex
W2050169742
Cited by
399
References
7
FWCI
14.41
Type
journal article
Language
en
Open access
gold

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