@article{17455fbc3f2449178f369de0e54f1043,
title = "Exploiting the CRISPR/Cas9 PAM constraint for single-nucleotide resolution interventions",
abstract = "CRISPR/Cas9 is an enabling RNA-guided technology for genome targeting and engineering. An acute DNA binding constraint of the Cas9 protein is the Protospacer Adjacent Motif (PAM). Here we demonstrate that the PAM requirement can be exploited to specifically target single-nucleotide heterozygous mutations while exerting no aberrant effects on the wildtype alleles. Specifically, we target the heterozygous G13A activating mutation of KRAS in colorectal cancer cells and we show reversal of drug resistance to a MEK small-molecule inhibitor. Our study introduces a new paradigm in genome editing and therapeutic targeting via the use of gRNA to guide Cas9 to a desired protospacer adjacent motif.",
author = "Yi Li and Saurabh Mendiratta and Kristina Ehrhardt and Neha Kashyap and White, {Michael A.} and Leonidas Bleris",
note = "Funding Information: This work was funded by the US National Institutes of Health (NIH) grants GM096271, CA170018, the US National Science Foundation (NSF) CAREER grant 1351354, the University of Texas at Dallas, and Robert Welch Foundation (I-1414). We would like to thank S. Lawson, M. Hasoon, T. Guinn and S. Lin for technical support. Publisher Copyright: {\textcopyright} 2016 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",
year = "2016",
month = jan,
day = "1",
doi = "10.1371/journal.pone.0144970",
language = "English (US)",
volume = "11",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "1",
}