Next Article in Journal
Elevated STAT3 Signaling-Mediated Upregulation of MMP-2/9 Confers Enhanced Invasion Ability in Multidrug-Resistant Breast Cancer Cells
Next Article in Special Issue
Application of CRISPR/Cas9 Technology to HBV
Previous Article in Journal / Special Issue
CRISPR/Cas9-Mediated Rapid Generation of Multiple Mouse Lines Identified Ccdc63 as Essential for Spermiogenesis
Article Menu
Issue 10 (October) cover image

Export Article

Open AccessReview
Int. J. Mol. Sci. 2015, 16(10), 24751-24771;

Minimizing off-Target Mutagenesis Risks Caused by Programmable Nucleases

Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
Institute for Integrated Cell Material Sciences (iCeMS), Kyoto University, Yoshida Ushinomiya-cho, Sakyo-ku, Kyoto 606-8507, Japan
These authors contributed equally to this work.
Author to whom correspondence should be addressed.
Academic Editor: Izuho Hatada
Received: 26 August 2015 / Revised: 2 October 2015 / Accepted: 8 October 2015 / Published: 16 October 2015
(This article belongs to the Special Issue Genome Editing)
Full-Text   |   PDF [607 KB, uploaded 16 October 2015]   |  


Programmable nucleases, such as zinc finger nucleases (ZFNs), transcription activator like effector nucleases (TALENs), and clustered regularly interspersed short palindromic repeats associated protein-9 (CRISPR-Cas9), hold tremendous potential for applications in the clinical setting to treat genetic diseases or prevent infectious diseases. However, because the accuracy of DNA recognition by these nucleases is not always perfect, off-target mutagenesis may result in undesirable adverse events in treated patients such as cellular toxicity or tumorigenesis. Therefore, designing nucleases and analyzing their activity must be carefully evaluated to minimize off-target mutagenesis. Furthermore, rigorous genomic testing will be important to ensure the integrity of nuclease modified cells. In this review, we provide an overview of available nuclease designing platforms, nuclease engineering approaches to minimize off-target activity, and methods to evaluate both on- and off-target cleavage of CRISPR-Cas9. View Full-Text
Keywords: CRISPR Cas9; genome editing; mutagenesis; off-target effect CRISPR Cas9; genome editing; mutagenesis; off-target effect

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Share & Cite This Article

MDPI and ACS Style

Ishida, K.; Gee, P.; Hotta, A. Minimizing off-Target Mutagenesis Risks Caused by Programmable Nucleases. Int. J. Mol. Sci. 2015, 16, 24751-24771.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top