Phan Toan Thang

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

Published date : 29 Aug 2018

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.

type
Book/Book Chapter
journal
Methods in Molecular Biology: Zinc Finger Proteins, 2018;1867:141-164. doi: 10.1007/978-1-4939-8799-3_11

Multidimensional genome-wide analyses show accurate FVIII integration by ZFN in primary human cells

Published date : 22 Dec 2015

Costly coagulation factor VIII (FVIII) replacement therapy is a barrier to optimal clinical management of hemophilia A. Therapy using FVIII-secreting autologous primary cells is potentially efficacious and more affordable. Zinc finger nucleases (ZFN) mediate transgene integration into the AAVS1 locus but comprehensive evaluation of off-target genome effects is currently lacking. In light of serious adverse effects in clinical trials which employed genome-integrating viral vectors, this study evaluated potential genotoxicity of ZFN-mediated transgenesis using different techniques.

type
Journal Paper
journal
Molecular Therapy 2015 Dec 22. doi: 10.1038/mt.2015.223
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