The clock is ticking for . He wants to use CRISPR gene editing to correct the genes of his friend鈥檚 13-year-old son.
The boy, Gavriel, has Duchenne muscular dystrophy, a genetic disease in which muscles degenerate. Breathing and heart problems often start by the time people with the condition are in their early twenties. Life expectancy is about 25 years.
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By the standards of science, the field of CRISPR gene editing is moving at a lightning fast pace. Although the technique was only invented a few years ago, it is already being used for research by thousands of labs worldwide to make extremely precise changes to DNA. A handful of people have already been treated using therapies enabled by the technology, and last week an effectively endorsed the idea of gene editing embryos. It is too soon to try the technique out, but the summit concluded that basic research on embryos should be permitted, alongside a debate on how we should use the technology.
But for people like Cohn, progress can鈥檛 come fast enough.
Need for speed
Gavriel was diagnosed at age 4. He has already lost the use of his legs but still has some movement in his upper body, and uses a manual wheelchair. Cohn, a clinician at the Hospital for Sick Children in Toronto, estimates that he has three years to develop and test a CRISPR-based treatment if he is to help Gavriel.
Muscular dystrophy is caused by a faulty gene for the protein dystrophin, which holds our muscles together. Gavriel has a duplicated version of the gene. This week, Cohn鈥檚 team published a paper describing how they grew Gavriel鈥檚 cells in a dish and used CRISPR gene-editing techniques to snip out the duplication. With the duplication removed, his cells produced normal dystrophin protein.
Cohn says he plans to test the approach in mice with Gavriel鈥檚 exact mutation before he applies for permission to try it in the boy. He鈥檚 trying to balance speed and safety but he says the research in human cells is so new that he has many unanswered questions. 鈥淭hat鈥檚 what I鈥檓 losing sleep over.鈥�
鈥淚 think the issue of going from mouse to human has been one of the most difficult of all,鈥� says Barry Coller at the Rockefeller University in New York City. 鈥淚f the only model is the mouse then you have to make this very, very big leap鈥�.
Balancing act
Coller would prefer to see Cohn demonstrate that the system works in primates, but Cohn doesn鈥檛 think there will be time. 鈥淚鈥檓 going to think carefully with regulatory people, ethics, industry partners. I have a whole team that is ready to sit down with me to really think through what the best and safest approach is.鈥�
Should the approach work in animals, there are ways to get it into human cells. A gene therapy trial for muscular dystrophy is already under way and involves delivering the corrected gene inside an inactivated virus. This could be repurposed to deliver the CRISPR system instead.
Cohn鈥檚 quest comes as last week鈥檚 committee effectively put us on a path that could see germline gene editing 鈥� that involving embryos, sperm or eggs 鈥� happening in people in some countries just decades from now.
Germline editing is controversial because the changes are passed on to future generations. Earlier this year, a team in China published the results of its attempt to modify human embryos using CRISPR, for research purposes only. Several other groups were rumoured to be doing similar work.
Editing embryos
While such studies are legal in many countries, concerns about this kind of work led to calls in March for a voluntary ban on editing human embryos. This is what prompted the national academies of science in many countries 鈥� including the US, UK and China 鈥� to organise last week鈥檚 summit.
A statement released by the summit鈥檚 organising committee said it would be irresponsible to attempt germline editing in humans until it can be done safely, and until there is wide agreement on what it should be used for. This point is still a long way off.
鈥淗owever, as scientific knowledge advances and societal views evolve, the clinical use of germline editing should be revisited on a regular basis,鈥� said the committee, which contained both biologists and ethicists.
The statement, released at the end of the International Summit on Human Gene Editing in Washington DC, calls for everyone from scientists to members of the public to start discussing what constitutes acceptable use of the technology. Countries should then introduce regulations that allow those applications while banning others considered unacceptable. For instance, some might approve of germline editing to reduce a person鈥檚 risk of Alzheimer鈥檚 disease, but draw the line at changing skin colour.
Journal reference: The American Journal of Human Genetics, http://dx.doi.org/10.1016/j.ajhg.2015.11.012
Image credit: Kerry Rosenfeld
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