The Koyal Group Info Mag News: Scientific split - the

human genome breakthrough dividing former

colleagues

The money men have moved in on a new technique for editing the human genome that
promises to revolutionise the way many human diseases will be treated in the future. But Big
Money has in the process divided a scientific community into two competing camps.

Some might see it has healthy scientific rivalry spilling over into commercial competition which
could ultimately speed up medical innovation. But behind closed doors there is a desperate
race to establish scientific and commercial priority over what could be the scientific discovery
and intellectual property of the decade.

On the one side is a consortium of world-class researchers led by French-born Professor
Emmanuelle Charpentier who made a key discovery behind the Crispr gene editing technique
and has been promised $25m (16m) by a group of venture capitalists to commercialise her
invention for medical use.

On the other side is her former colleague and the co-discoverer of the gene-editing process,
Professor Jennifer Doudna of the University of California, Berkeley, who has joined a rival
consortium of researchers with $43m in venture capital to advance the Crispr technique into
the clinic.

Each group has recruited a formidable panel of senior scientists as advisers. The Charpentier
team, called Crispr Therapeutics, includes Nobel Laureate Craig Mello, the co-discoverer of a
gene-silencing technique known as RNAi, and Daniel Anderson of the Massachusetts Institute
of Technology, who was the first person to show that Crispr can cure a genetic disease in an
adult animal.

Meanwhile the Doudna team, known as Editas Medicine, includes the Harvard geneticist
George Church, a pioneer in synthetic biology, and Feng Zhang of MIT and the Broad Institute,
who successfully managed to get Crispr to work in human cells and was this month awarded
the first US patent on the technique much to the dismay of Professor Charpentier.

I have to be careful what I say here. It is very surprising. But the fundamental discovery
comes from my laboratory and no-one has told me that they have scooped me, Professor
Charpentier told The Independent.

Be certain that this discovery did not happen only by chance. I have been thinking, defending
and carrying this study from Austria to Sweden and now Germany, she said.

Patent attorneys are now pouring over the rival patent applications, in particular the claims
relating to who has priority over a key element of the Crispr technique called Cas9, a bacterial
gene for an enzyme that snips both strands of the DNA double helix at the same place a key
feature of the gene-editing process.

Professor Charpentier said that she identified Cas9, the most important fundamental discovery
behind Crispr (pronounced crisper), when she worked at Umea University in Sweden, before
she had teamed up with Professor Doudna to co-author a scientific paper on Crispr-Cas9
published in August 2012 in the journal Science.

Professor Charpentier, who is now at the Hannover Medical School in Germany, said that Cas9
was in fact described for the first time in an earlier scientific paper, published in Nature in
March 2011, under its former name of Csn1, which she had isolated from the bacterium
Steptococcus pyogenes.

I was the scientist who described the technology and I kept the intellectual property when I
was in Sweden.Editas does not have access to the intellectual property of the patent where
Im the co-inventor, Professor Charpentier said.

I made the decision to do something in Europe and I made the decision not to do something
with Editas Medicine. Im trying to remain true to myself.The aim is to use Crispr-Cas9 as a
kind of genetic medicine to treat serious diseases. The point about Cas9 is that it works in
every cell and in every organism tested its mind blowing, she said.

For her part, Professor Doudna said there is room for both camps to develop new medical
therapies based on Crispr-Cas9.

Emmanuelle and I are excited to see this platform employed to help patients, and there are
of course many different targets and strategies to be taken, providing opportunities for
multiple companies in this space, Professor Doudna said.

In addition to start-ups, many existing companies are also interested in using the technology
for various applications that extend beyond human therapeutics. I expect that the commercial
landscape will continue to evolve as the technology matures, she said.

The main barrier to using Crispr-Cas9, however, will be its safe and efficient delivery to the
cells and tissues that need the genetic therapy. Professor Mello believes that the first
treatments are likely to involve the genetic manipulation of stem cells in the laboratory,
before transplantation back into the affected parts of the body.

Delivery to cells within the context of the whole body, brain or other organ is very difficult
and inefficient This is why Crispr therapies will no doubt be limited for the foreseeable future
to applications where stem cells can be modified one, or a few, at a time and then
reintroduced after double checking that only the intended change was made, Professor Mello
said.

WHAT IS CRISPR?

The human genome consists of a long sequence of "letters" written in the code of the genetic
alphabet - the three billion base-pairs of the DNA molecule. The gene-editing technique known
as Crispr-Cas9 is able for the first time to delete or swap any of these letters, right down to
changing a single base pair at any designated place in the genome.

Crispr, which stands for clustered regularly interspaced short palindromic repeats, was
originally discovered as a kind of immune system in bacteria to defend against invading
viruses. Its potential for editing the genomes of animals, including humans, only came with the
discovery of the Cas9 gene, an enzyme for cutting both strands of DNA, found in the bacterium
Streptococcus pyogenes.

The commercial applications of Crispr, which could extend to treating genetic diseases and
cancer, will depend to a great extent on Cas9 and who owns the intellectual property on this
part of the invention. This is why patent disputes are likely to focus on who did what and when
in terms of the Cas9 discovery. Emmanuelle Charpentier of Hannover Medical School in
Germany and Jennifer Doudna of the University of California, Berkeley are both named as co-
inventors on one patent.