Romain Rouet, Benjamin A Thuma, Marc D Roy, Nathanael G Lintner, David M Rubitski, James E Finley, Hanna M Wisniewska, Rima Mendonsa, Ariana Hirsh, Lorena de Oñate, Joan Compte, Thomas J Mclellan, Justin Bellenger, Xidong Feng, Alison Varghese, Boris A Chrunyk, Kris A Borzilleri, Kevin D Hesp, Kaihong Zhou, Nannan Ma, Meihua Tu, Robert Dullea, Kim F Mcclure, Ross C Wilson, Spiros Liras, Vincent Mascitti, Jennifer A Doudna
CRISPR-Cas RNA-guided endonucleases hold great promise for disrupting or correcting genomic sequences through site-specific DNA cleavage and repair. However, the lack of methods for cell- and tissue-selective delivery currently limits both research and clinical uses of these enzymes. We report the design and in vitro evaluation of S. pyogenes Cas9 proteins harboring asialoglycoprotein receptor ligands (ASGPrL). In particular, we demonstrate that the resulting ribonucleoproteins (Cas9-ASGPrL RNP) can be engineered to be preferentially internalized into cells expressing the corresponding receptor on their surface...
April 18, 2018: Journal of the American Chemical Society