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Ever since scientists began decoding the human genome in 1990, doctors have dreamt of a new era of medicine where illness could be treated — or even cured — by fxing flaws in a person’s DNA. Rather than using medicine to fight disease, they would be able to hack biology to combat sickness at its source.
The dream started to become a reality in 2013, when researchers demonstrated how a gene editing technique, known as Crispr-Cas9, could be used to edit living human cells, raising the possibility that a person’s DNA could be altered much as text is changed by a word-processor.
Now, two biotech companies say they plan to start testing the technology in humans as early as this year.
Crispr Therapeutics has already applied for permission from European regulators to test its most advanced product, code-named CTX001, in patients suffering from beta-thalassaemia, an inherited blood disease where the body does not produce enough healthy red blood cells. Patients with the most severe form of the illness would die without frequent transfusions.
The Switzerland-based company says it also plans to seek a greenlight from the US Food and Drug Administration this year so it can trial CTX001 in people with sickle cell disease, another inherited blood disorder.
Editas Medicine, Crispr’s US-based rival, says it plans to apply for permission from the FDA in the middle of the year so it can test one of its one of its own Crispr gene-editing products in patients with a rare form of congenital blindness that causes severe vision loss at birth. If the FDA agrees, it should be able to commence trials within 30 days of the application.
If those trials are successful, Crispr, Editas and a third company, Intellia Therapeutics, say they plan to study the technique in humans with a range of diseases including cancer, cystic fibrosis, haemophilia and Duchenne muscular dystrophy.
In China, where regulators have taken a more lenient approach to human trials, several studies are already under way, although they have yet to produce any conclusive data.
Crispr-Cas9 is best thought of as two technologies that make gene editing possible: Cas9 acts as a pair of “molecular scissors” that can snip strands of DNA, removing faulty genetic material and creating space for functioning genes to be inserted. Crispr is a kind of genetic GPS that guides those scissors to the precise location.
Katrine Bosley, chief executive of Editas, says the field of gene editing is moving at “lightning speed”, but that the technique will at first be limited to illnesses “where there are not other good options”.
That is because, as with any new technology, scientists and regulators are not fully aware of the safety risks involved. “We want it to be as safe as it can, but of course there is this newness,” says Ms Bosley.
Gene editing milestones
Francisco Mojica at the University of Alicante, Spain becomes the first researcher to discover Crispr sequences
Alexander Bolotin at the French National Institute for Agricultural Research observes Cas9 genes in the bacteria Streptococcus thermophilus
Scientists at Danone study how Crispr techniques can help Streptococcus thermophilus, widely used in commercial yoghurt making, ward off viral attacks
Biochemists Jennifer Doudna and Emmanuelle Charpentiere show that Crispr can be used to edit DNA in test tubes
Feng Zhang of the Broad Institute reports using Crispr to edit DNA in human cells, opening the door for the tool to be used in medicine
Crispr is used to edit the genomes of everything from flies to mice
British scientists use Talen gene editing to treat a child’s leukaemia
Still, Ms Bosley points out that of the more than 6,000 genetic disorders, which are the most obvious candidates for gene editing, roughly 95 per cent are untreatable. This provides plenty of areas for companies like hers to explore.
Although Crispr-Cas9 has not yet been trialled in humans in Europe or the US, the technology has already benefited medical research greatly by speeding up laboratory work. It used to take scientists several years to create a genetically modified mouse for their experiments, but with Crispr-Cas9 these “transgenic” mice can be produced in a few weeks.
Cellectis, a French biotech group, has used an older gene-editing technique known as Talen, to create a pioneering blood cancer treatment known as chimeric antigen receptor therapy or Car-T, which is currently being tested in humans.
Car-T products are already on the market, but rely on an expensive and laborious process that involves extracting a person’s white blood cells, transporting them by aeroplane to a lab where they are re-engineered to attack cancer, before returning them and inserting them into the patient.
Cellectis hopes its approach of using gene editing to alter the cells will cut out this lengthy re-engineering process.
Some proponents of Crispr-Cas9 dismiss the Talen technique as old, slow and expensive, but André Choulika, Cellectis chief executive, disagrees.
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“We’re not talking about iPhones here,” he says. “Maybe [Crispr] is a new technology, it’s easy to design and it’s cheap, but who cares? This is not what the patient needs. The patient needs a super-active, super-precise product.”
Amid the excitement, the nascent field of gene editing has been hampered by several setbacks. Editas had hoped to start human trials earlier, but was forced to move the date back after it encountered manufacturing delays. Crispr has lost several key executives in recent months, while Cellectis had to suspend its first trial briefly last year after a patient died.
Meanwhile, a bitter patent dispute over which academic institution discovered Crispr-Cas9, and therefore which biotech company has the rights to the patents, has cast a pall over gene editing.
The field is in its infancy and progress in any new area of science is never smooth. If gene editing lives up to its promise, it could one day save or dramatically change the lives of tens of millions of patients with hitherto untreatable diseases.