Reports

Stephan Emmerth

Stephan Emmerth

PhD | Director Therapeutic Innovation and BaseLaunch


Tel. +41 61 295 50 17

stephan.notexisting@nodomain.comemmerth@baselarea.notexisting@nodomain.comswiss
report Life Sciences
DNA editing. (Img: Lightspring/shutterstock)

DNA editing. (Img: Lightspring/shutterstock)

28.01.2015

Therapeutic gene editing is taking off – and Basel is right in the middle

Very rarely can a scientist claim to have had a fundamental and game-changing impact in his field and beyond. But Jennifer Doudna from University of California, Berkeley, and Emmanuelle Charpentier, who was working at the University of Umeå in Sweden at the time, can claim just that. In mid-2012, when they published their discovery of an RNA-programmable tool (termed CRISPR for Clustered Regularly Interspaced Short Palindromic Repeats) which allowed DNA to be cleaved in a very targeted and extremely efficient manner, they created a stir, because this tool could potentially also be used for RNA-programmable genome editing. And only months later, this is exactly what George Church from Harvard and Feng Zhang from the Broad Institute of MIT and Harvard showed in two independent publications: CRISPR could be used to edit the genome of potentially any organism, from yeast to man, whether to introduce new mutations, to correct disease-causing mutations or to insert or remove whole sections of DNA in the genome, and all of this in no time at all. After this the biomedical community was jumping with excitement, and scientists were describing CRISPR as the “holy grail” of genetic engineering and a «jaw-dropping» breakthrough in the fight against genetic disease.

A new era in gene editing
It was not that genomes had not been editable until then. But for higher eukaryotes, such as mice, monkeys, dogs or also human cells, it was a slow, painstaking and expensive process that could potentially take months if not years. But with CRISPR it was possible for the first time to edit the genome very precisely and at unprecedented speed and very little cost. The research community quickly embraced CRISPR as a research tool to engineer custom transgenic lab animals in a matter of weeks—saving about a year's worth of work. This not only enables new model organisms to be established in a very short time for many hitherto hard to treat diseases, such as Alzheimer’s, multiple sclerosis, autism, certain forms of cancer, but also allows cell lines to be edited for drug screening or new approaches to be explored for treating HIV. It might also be possible to for example correct the chromosomal abnormality associated with Down syndrome early in a pregnancy, to reintroduce susceptibility to herbicides in resistant weeds, to bring back extinct animal species and very much more.

On the road to commercialization
From the outset, of course, it was clear that CRISPR would also attract a lot of interest from the biotech world, which is also where Basel enters into the story. So far, three therapeutic biotech companies have been formed around CRISPR, two of them having links to Basel. The first of these was Editas Medicine from Boston, which was launched in late 2013 with $43 million in venture capital from Flagship Ventures, Thirdrock Ventures, Polaris Partners and the Partners Innovation Fund. A few months later, the Basel office of Versant Ventures announced a Series A investment of $25 million to start up CRISPR Therapeutics with headquarters in Basel. And in late 2014, Atlas Ventures and Novartis announced the formation of Intellia Therapeutics (although it had already existed in stealth mode for almost two years) with a Series A investment round of $15 million.

And just recently Novartis also concluded the first biotech-pharma licensing deal in this area with Intelllia, for exclusive rights for ex vivo engineering of chimeric antigen receptor (CAR) T cells (another hot topic in biotech/pharma research these days) and the right to develop a number of targets for ex vivo editing of hematopoietic stem cells. Ex vivo applications, in which cells are extracted from patients and manipulated outside the patient’s body and then re-infused, will very likely be among the first treatments to be developed for Editas Medicine and CRISPR Therapeutics, as this can be addressed with the technology as it stands today. The companies expect clinical trials to begin in as little as three years.

Challenges ahead
One of the big challenges, however, will be to make CRISPR a technology to treat genetic diseases of any kind with a one-time fix that can «edit» out genetic abnormalities and cure disease at the genetic level, potentially in a single treatment, in vivo. But for this to happen, ways have to be figured out for safely and effectively delivering a gene-editing drug into the body, which is still a very big hill to climb.

And there is another issue: The patent situation is in a state of some confusion. The first patent issued went to the Broad Institute of Harvard and MIT and was licensed by Editas Medicine. However, after that patent was granted, Jenifer Doudna, originally one of the co-founders of Editas Medicine, broke off her relationship with the company, and licensed her intellectual property - in the form of her own pending patent - to Intellia Therapeutics. And to confuse the issue further, Emmanuelle Charpentier, who claims that «the fundamental discovery comes from my laboratory», licensed her own rights in the same patent application to CRISPR Therapeutics.

So there appears to be a lot of work for patent lawyers to sort out in the next few months. But despite all the legal wrangling, CRISPR will without doubt continue to transform biomedical research in a way very seldom seen before and be transformative in the way we treat genetic diseases.

More information
General
Youtube Video «Genome Editing with CRISPR-Cas9»
New York Times article «A Powerful New Way to Edit DNA»
The Independent article «The more we looked into the mystery of Crispr, the more interesting it seemed»

Companies
Editas Medecine
CRISPR Theraeputics
i-net article «$25 million in series A financing for Basel-based CRISPR Therapeutics»
Intellia Therapeutics
collaboration with Novartis:
FierceBiotech article «Novartis adopts a CRISPR-Cas9 partner and jumps into the hot new R&D field»
FierceBiotech article «Novartis joins Atlas in launching a CRISPR Cas biotech with a $15M bankroll»
Xconomy article «CART + CRISPR = 1st-Of-Its-Kind Biotech Deal From Novartis, Intellia»

Patents
MIT Technology Review article «Who Owns the Biggest Biotech Discovery of the Century?»
Independent article «Scientific split - the human genome breakthrough dividing former colleagues»
Fiercebiotech article «A biotech war is brewing over control of the revolutionary CRISPR-Cas9 tech»

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