January 20, 2022

The Yan Zhang lab publishes a research paper in Molecular Cell

Cas11 enables genome engineering in human cells with compact CRISPR-Cas3

Cas11, a product of internal translation in bacteria, is an essential component of CRISPR-Cas3 that enables CRISPR-Cas3 genome editing in human cells.

In an article published in Molecular Cell, researchers from the laboratory of Dr. Yan Zhang report their development of novel miniature CRISPR-Cas3 gene editors for targeted large-scale genome manipulation in human cells. As part of this work they discovered a "hidden" bacterial internal translation product, Cas11—a previously overlooked but essential component of the CRISPR-Cas3 machinery from bacteria species like Neisseria lactamica. In human cells Cas11 serves as the key enabler to implement a set of evolutionarily divergent CRISPR-Cas3 editors with favorable features including high efficiency, distinct PAM preferences, and ease of manufacturing as ribonucleoprotein (RNP) complexes. Findings from this paper pave the way for applying CRISPR-Cas3 to dissect regulatory elements and structural variants that impact human diseases. Ph.D. student Renke Tan and master's student Ryan Krueger are the paper’s first authors, and Dr. Yan Zhang and Dr. Zhonggang Hou are the corresponding authors.

"Discovery of a 'hidden gem' enables gene editing with a small but mighty CRISPR-Cas3 system" by Kelly Malcom, Michigan Medicine
Research paper in Molecular Cell