Who will get Custody?

(May 23rd, 2014) Many scientists believe CRISPR, a new gene editing tool, will revolutionise the way we think about treating many human diseases. However, its commercial value has not gone unnoticed, and an interesting duel is developing between two rival companies.

CRISPR (pronounced “crisper”) - which stands for Clustered Regularly Interspaced Short Palindromic Repeats – is part of a bacterial immune system to fight viral infections. The initial discovery didn’t warrant a second look, but when researchers figured out what Cas9 – the main enzyme involved in the process – can do, it opened the door to a whole new gene editing tool. It turns out Cas9, initially discovered in the bacterium Streptococcus pyogenes, is able to cut both strands of DNA, allowing researchers to introduce specific mutations, including deletions, substitutions or insertions, into the genome (see also a Journal Club with Martin Jinek, University of Zürich, in the current issue of Lab Times).

Not surprisingly, this is ideal patent material: the CRISPR-induced new DNA sequences certainly tick the “novelty” box and nobody can argue about its “usefulness”. For this reason, the CRISPR system is likely to be the underpinning element in many patent applications, from genes and proteins, to transgenic animals and plants produced as a result of its application.

There is still a lot of work to be done though, says Emmanuelle Charpentier, from the Helmholtz Centre for Infection Research in Braunschweig, Germany, and one of the authors of the 2012 landmark paper defining the CRISPR system for the first time. “I believe that the CRISPR/Cas9 system has the potential to be translated into gene medicines for the treatment of certain genetic diseases, [but] it will take, probably 3 to 4 years, until we see the first products in early clinical trials.”

Despite the current constraints, future commercial CRISPR applications have the potential to treat many genetic diseases, cancer and others. “Probably mostly suited, at least at the get-go, are diseases which have a dominant trait and therefore are addressable by knocking out strategy. Also, diseases which do not require a systemic delivery of the CRISPR/Cas9 components are preferable,” adds Charpentier.

Progress will depend on who owns Cas9’s intellectual property and this is where problems have already started. Fighting for control are former colleagues Charpentier and Jennifer Doudna, from the University of California, Berkeley, USA, who was also involved in the high-profile 2012 paper. Both were named as co-inventors in the Cas9 patent, but have since gone their separate ways to found multinational rival companies.

Based on Charpentier’s know-how, CRISPR Therapeutics recently received a $25m (£16m) endorsement by California-based Versant Ventures, a group of venture capitalists, to adapt her discovery for medical purposes. “The management team, namely Rodger Novak,” says Charpentier, “selected the founders because of their highly complementary skill sets – be it in the translation of gene editing technologies (Matthew Porteus), RNA delivery (Daniel Anderson), gene silencing (Craig Mello), stem cell biology (Chad Cowan), or myself as an RNA biologist with deep expertise in the CRISPR system.”

On the other side is rival consortium Editas Medicine and Doudna, who have managed to gather $43m in venture capital to further the use of the CRISPR system. The team includes, among others, geneticist George Church, chemist David Liu and neuroscientist Feng Zhang.

Keeping scientists on the edge of their seats, the conflict between the two companies is obvious. CRISPR Therapeutics maintain they have secured the rights to the foundational intellectual property covering the use of CRISPR/Cas9 genome editing in human therapeutics, but nevertheless the first US patent for CRISPR application was awarded to Editas member Feng Zhang from MIT and The Broad Institute, after his team showed that CRISPR works in human cells. The race for ownership is expected to continue.

Despite all this, concludes Charpentier, “A more important thought is that one hopes that the CRISPR technology will have contributed to the treatment of diseases which, as of now, have no or only very limited treatment options.” However, for some, the main question remains unanswered: is it really worth maintaining the restrictions imposed by intellectual property rules, not to mention the waste of time and money, or would it not be better to combine efforts to speed up CRISPR-based treatments?

Alex Reis

Picture: Editas Medicine & CRISPR Therapeutics

Last Changes: 07.01.2014