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New CRISPR Protein Slices through Genomes, Patent Problems

Scientists predict an explosion of new genome-editing methods.
September 25, 2015

Scientists in Boston have come up with a twist on an important method for “editing” genomes that could give researchers added control over the DNA of living things and influence a raging patent dispute over the powerful techniques.

Feng Zhang

Feng Zhang, a researcher at the Broad Institute of MIT and Harvard, reported today in the journal Cell that he had developed a replacement for a key component of the genome-engineering system commonly known as CRISPR-Cas9.

The gene-editing technology, which snips DNA at precise locations, has swept through science labs because it provides a versatile, potent way to engineer the DNA of bacteria, plants, and humans. It is allowing scientists to broadly reimagine how they study everything from Alzheimer’s disease to biotech crops.

The work by Zhang’s team, carried out this year, shows that the cutting protein Cas9 can be replaced by a different protein, Cpf1, which he says will also work as a versatile editing tool. In a carefully crafted press release, Broad chief Eric Lander said the system “represents a new generation of genome editing technology” that has “dramatic potential to advance genetic engineering.”

The background for the Broad announcement is a bruising patent fight with the University of California, Berkeley, over who invented the first CRISPR editing tools, in particular Cas9 (see “Who Owns the Biggest Biotech Discovery of the Century?”). The U.S. Patent Office is weighing a decision to intervene in the case (see “CRISPR Patent Fight Now a Winner-Take-All Match”).

The new system, because it has a different cutting protein, could offer a way around the legal quagmire. “The greatest value may be more in terms of the patent landscape than a scientific advancement,” says Dan Voytas, a genome-editing researcher at the University of Minnesota.

The stakes are high as startups race to develop gene editing as a basis for possible medical treatments. Editas Medicine, which is connected with Feng’s lab, raised an additional $120 million in August. Intellia, a competitor connected to the Berkeley team, raised $70 million this month.

CRISPR is based on a natural system some bacteria use to defend against viruses by shredding their invading genes. In the laboratory, it’s been adapted as a tool that consists of two key components: a short stretch of RNA that lines up with a specific gene, and then a cutting protein that moves in to snip the gene open.

Eugene Koonin, a researcher at the National Institutes of Health who coauthored the paper in Cell, said the current work began with computer predictions of proteins in bacteria that might serve a similar cutting role as Cas9. “It is indeed a new system that is substantially different than the previously known one,” he says.

Scientists not involved in the work said the new system was likely to fill a limited role in what is a growing toolbox of DNA-editing techniques. George Church, who develops genomics technology at Harvard University, says the system has features that could be useful in cells that don’t divide, including nerves and most other cells in our body, which are typically harder to edit. “There is a niche market for a collection of different proteins so that cuts can be placed anywhere in the genome,” he says.

Broad and Feng have won more than 10 key patents on CRISPR genome editing using Cas9. However, they have been losing the fight to win public credit for the invention, which the news media and prize-giving organizations have instead handed to Jennifer Doudna of Berkeley and Emmanuelle Charpentier of the Helmholtz Center for Infection Research in Germany for work originally published in 2012.

This week, Reuters named Doudna and Charpentier among likely winners of a Nobel Prize in October.

Broad and MIT continue to lobby for a different view of scientific events. This month, Robert Desimone, director of MIT’s McGovern Institute for Brain Research, where Feng holds an appointment, wrote to the Economist correcting that magazine’s account of how CRISPR-Cas9 was invented, saying the Berkeley team had used “no cells, no genomes and no editing.”

The discovery of how to manipulate the CRISPR system is probably only the beginning of a new era of precision genome editing, Feng says, with many new approaches under development. “Nature has had billions of years to create these tools,” he says. “We would like to turn over as many rocks as we can find.”

Patent applications have been filed on the new technology. In its release, the Broad Institute said the new form of CRISPR editing would be available to scientists and widely licensed to companies that sell systems and chemicals for research. The organization was silent on which company might receive rights to use the technology in developing new medical treatments.

Feng said it was “too early to know the specifics” but said rights to the new technology wouldn’t necessarily belong to Editas, the company he cofounded.

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