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Integrated Multimodal Evaluation of Genotoxicity in ZFN-Modified Primary Human Cells. | LitMetric

Integrated Multimodal Evaluation of Genotoxicity in ZFN-Modified Primary Human Cells.

Methods Mol Biol

Division of Medical Sciences, Laboratory of Applied Human Genetics, Humphrey Oei Institute of Cancer Research, National Cancer Centre, Singapore, Republic of Singapore.

Published: July 2019

AI Article Synopsis

Article Abstract

Iatrogenic adverse events in clinical trials of retroviral vector-mediated gene-corrected cells have prioritized the urgent need for more comprehensive and stringent assessment of potentially genotoxic off-target alterations and the biosafety of cells intended for therapeutic applications. Genome editing tools such as zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced palindromic repeats (CRISPR)-Cas9 nuclease systems are being investigated as safer and efficient alternatives for site-directed genome modification. Using site-specific integration into the AAVS1 locus of primary human cells as an example, we present an integrated approach to multimodal investigation of off-target alterations and an evaluation of potential genotoxicity induced by ZFN-mediated integration of a therapeutic transgene.

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Source
http://dx.doi.org/10.1007/978-1-4939-8799-3_11DOI Listing

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