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In vivo CRISPR/Cas9 targeting of fusion oncogenes for selective elimination of cancer cells
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In vivo CRISPR/Cas9 targeting of fusion oncogenes for selective elimination of cancer cells
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Journal Article
In vivo CRISPR/Cas9 targeting of fusion oncogenes for selective elimination of cancer cells
2020
Overview
Fusion oncogenes (FOs) are common in many cancer types and are powerful drivers of tumor development. Because their expression is exclusive to cancer cells and their elimination induces cell apoptosis in FO-driven cancers, FOs are attractive therapeutic targets. However, specifically targeting the resulting chimeric products is challenging. Based on CRISPR/Cas9 technology, here we devise a simple, efficient and non-patient-specific gene-editing strategy through targeting of two introns of the genes involved in the rearrangement, allowing for robust disruption of the FO specifically in cancer cells. As a proof-of-concept of its potential, we demonstrate the efficacy of intron-based targeting of transcription factors or tyrosine kinase FOs in reducing tumor burden/mortality in in vivo models. The FO targeting approach presented here might open new horizons for the selective elimination of cancer cells.
Fusion oncogenes (FO) are common in cancers, but specific targeting of these chimeric genes are challenging. Here the authors report a CRISPR/Cas9 strategy that targets two intronic regions to disrupt the FOs in cancer cells and show that this approach reduces tumour growth and prolongs survival in animal models of cancer.
Publisher
Nature Publishing Group UK,Nature Portfolio
Subject
/ 13/106
/ 13/2
/ 13/51
/ 42/41
/ 42/44
/ 64
/ 64/60
/ Animals
/ Cell Proliferation - genetics
/ CRISPR-Cas Systems - genetics
/ Doxorubicin - therapeutic use
/ Fusion Proteins, bcr-abl - genetics
/ Humanities and Social Sciences
/ Humans
/ Oncogene Proteins, Fusion - genetics
/ RNA, Guide, CRISPR-Cas Systems - metabolism
/ Science
