Information about CRISPR-Cpf1 (Cas12a) systems

In September 2015, a team including the scientist who first harnessed the revolutionary CRISPR-Cas9 system for mammalian genome editing published findings that identified a different CRISPR system, called CRISPR-Cpf1 (now -Cas12a), with the potential for even simpler and more precise genome engineering.

In a study published in Cell, Feng Zhang and his colleagues at the Broad Institute of MIT and Harvard and the McGovern Institute for Brain Research at MIT, with co-authors Eugene Koonin at the National Institutes of Health, Aviv Regev (formerly of the Broad Institute and the MIT Department of Biology, and now at Genentech), and John van der Oost at Wageningen University, described the unexpected biological features of this system and demonstrated that it can be engineered to edit the genomes of human cells.

In April 2016 the Zhang team in collaboration with the University of Tokyo's Osamu Nureki and Hiroshi Nishimasu announced the structure of the new AsCpf1 enzyme in complex with target DNA, a view that provides some further guidance about how Cpf1 works. The structure provides insights into why Cpf1 leaves its target with staggered ends (as opposed to the blunt end cuts of Cas9), information that could help researchers engineer new Cpf1-based CRISPR gene editing tools.

In February 2017 the European Patent Office (EPO) announced it intends to grant its first CRISPR-Cpf1 patent to the Broad Institute, MIT, and Harvard University, based on a patent application filed in June 2015.

This patent adds to a growing international landscape of intellectual property around CRISPR. Several Cpf1 patent applications are pending in the United States, each describing various methods that rely on the system first published by Zhang and collaborators in Cell in September, 2015. These include applications from the Broad Institute as well as from other organizations, such as an application filed by Caribou Biosciences, Inc. and now assigned to Pioneer Hi-Bred International, Inc., a subsidiary of E. I. du Pont de Nemours and Company, (which has also received notice of allowance and will issue as US Patent No. 9,580,701 on Tuesday, February 28th based on USPTO application No. 15/238,464). The '701 patent claims are specific to the use of a certain -Cpf1 system having a DNA guide, or a guide that is a specified mixture of DNA and RNA. When first filed, this application only related to DNA guides for use with a CRISPR-Cas9 system. However, after the publication in Cell, showing that the RNA-guided, CRISPR-Cpf1 system could be engineered for site directed gene editing and use in eukaryotic cells, a further application was filed by Pioneer to add discussion and claims to use of these DNA guides with -Cpf1.