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CRISPR research is thriving, in spite of the intellectual property debate

by Alexandra Taylor Published on 15th Nov 2015

by Alexandra Taylor Published on 15th November 2015

Crispr has been heralded as the most important biotechnology breakthrough of the century. The battle over intellectual ownership of the platform has turned into an East Coast-West Coast rivalry of epic proportions. New developments published last month in Cell, however, are calling the relevance of this conflict into question. 

Revolutionary Technology

For the uninitiated, Crispr is part of some bacteria’s natural self-defense systems. When a virus invades, strands of RNA target its genome. A protein then cuts the viral DNA, disabling it. Scientists have harnessed this ability to edit the genomes of other organisms, including humans. While the technology is still very new, it has enormous implications for the future of medicine. 

In 2012, Dr. Jennifer Doudna of the University of California and Emmanuelle Charpentier of Umea University in Sweden published a paper in Science about the Crispr/Cas9 complex. Cas9 is the name of a protein used to cut the viral DNA once the bacterial RNA has targeted it. Doudna and Charpentier’s paper suggested that the Crispr/Cas9 system could be used to edit DNA, but did not lay out specific instructions for doing so. 

At the beginning of 2013, Dr. Feng Zhang, of the Broad Institute, and Dr. George Church, of Harvard Medical School, both published papers on the use of the Crispr/Cas9 complex in human cells. Because Crispr is a naturally occurring system, the mechanism itself cannot be patented. However, the modifications that allow researchers to apply CRISPR to human cells are considered proprietary technology. All the money lies in the potential medical applications, too numerous to count. 

Doudna and Charpentier first filed a patent application in May of 2012. Although Doudna was the first to publish on Crispr and the first to apply for a patent, so far, all patents have been granted to Zhang. 

While a dispute over the ownership of the CRISPR/Cas9 system rages on, a discovery published by Zhang’s lab last month in Cell may undermine much of the effort that both parties have poured into it. 

Tip of the Iceberg

Cpf1 is a protein that serves a function similar to Cas9 in human cells, but with some compelling variations. It is smaller, requires only one strand of RNA to target the DNA (as opposed to two), and cuts strands in a way that makes it easier for new DNA sequences to bind. It cuts further from the target site, allowing more room for error, and recognizes different sequences, giving researchers more options when selecting a protein. 

This discovery shows that the Crispr/Cas9 complex is not the only tool in the drawer. “We have the feeling it’s just the tip of the iceberg,” John van der Oost, a microbiologist and co-author on the paper, told Wired. There may be many such proteins like Cas9 and Cpf1 that can be used to perform a similar function with slight variations. As Zhang told Technology Review, “Nature has had billions of years to create these tools. We would like to turn over as many rocks as we can find.”

Intellectual Property 

What does this mean for intellectual ownership? The discovery of Cpf1 is likely to deflate Crispr/Cas9’s value as a proprietary technology. Zhang, Doudna, and Charpentier have all licensed their methods to startups in hopes of cashing in on their discoveries. While Zhang could patent Crispr/Cpf1 separately, the value of such licensing is now somewhat diminished. 

The beauty of the Crispr/Cas9 complex lies in its highly democratic nature: it is inexpensive and requires relatively little training to use. Doudna and Zhang have both made their technologies widely available to research institutions. Anyone looking to profit off of a therapeutic use could be required to pay a royalty to the patent holder. 

The potential for profit is so great that investors are largely undeterred by the uncertain patent situation. Research is pushing ahead. If more alternative protein complexes emerge—which, according to Zhang and colleagues, appears likely—the value of any individual patent will likely decrease. Patent owners will still be able to demand royalties, but the price will be lower than if CRISPR/Cas9 were the only complex on the market. 

While this discovery may call the value of the original patent into question, it is likely excellent news for potential therapies. The more versatile the genome editing toolkit, the more swiftly, safely, and diversely these discoveries can be translated into human health—at least, that is the hope.

Both Zhang and Doudna have put in the legwork to make Crispr systems accessible throughout the research community. The number of academic papers on gene editing has skyrocketed. CRISPR-related research is thriving in spite of the intellectual property debate. It will be interesting to see what develops in the coming years.