한빛사 논문
Daesik Kim,1,* Kevin Luk,2,* Scot A. Wolfe,2 and Jin-Soo Kim,1,3
1Center for Genome Engineering, Institute for Basic Science, Daejeon 34126, Republic of Korea;
2Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA;
3Department of Chemistry, Seoul National University, Seoul 08826, Republic of Korea
*These authors contributed equally to this article
To whom correspondence should be addressed. Jin-Soo Kim, Scot A. Wolfe
Abstract
Programmable nucleases and deaminases, which include zinc-finger nucleases, transcription activator-like effector nucleases, CRISPR RNA-guided nucleases, and RNA-guided base editors, are now widely employed for the targeted modification of genomes in cells and organisms. These gene-editing tools hold tremendous promise for therapeutic applications. Importantly, these nucleases and deaminases may display off-target activity through the recognition of near-cognate DNA sequences to their target sites, resulting in collateral damage to the genome in the form of local mutagenesis or genomic rearrangements. For therapeutic genome-editing applications with these classes of programmable enzymes, it is essential to measure and limit genome-wide off-target activity. Herein, we discuss the key determinants of off-target activity for these systems. We describe various cell-based and cell-free methods for identifying genome-wide off-target sites and diverse strategies that have been developed for reducing the off-target activity of programmable gene-editing enzymes.
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