CRISPR, a gene-editing technology, is exciting for its potential to cure genetic diseases, popular for its ease of use and controversial for experiments on human embryos, which have already happened in China.
Its power to manipulate genes, the underlying code of all life, is not in doubt. But its accuracy and reliability is, and new research out of Ontario and California on the technology’s emergency shut-down switches and built-in failsafes may bring greater precision and safety to a frontier medical science.
Discovered in the 1990s from studies on bacteria, with most progress in the last few years, CRISPR is the name for repeating bits of DNA that evolved as a kind of genetic immune system. By programming it in the lab and delivering it to a cell, CRISPR can activate or disable specific genes, which is ideal for treating diseases with discrete genetic causes, such as cystic fibrosis and some cancers.
Industrial investment has followed medical science, and both are booming. The first human study in the U.S., for cancer, was approved this year. And all five of 2016’s Gairdner Awards, famous as a precursor to the Nobel, went to CRISPR researchers, the first such sweep since genome sequencing in 2002. There is also a major patent battle, with a fortune in commercial applications at stake, that has pit Harvard and MIT against University of California and others.
But for all the hype, there are risks. CRISPR tends to hit unintended spots on the genome unpredictably. Leave it running on its own, and there is no telling what sort of genetic edits it might come up with, and what peril that might mean for the patient.
This is the Frankenstein problem of runaway biotech, and it has come true before, for example in Europe, where patients in a gene therapy trial using a similar technology to CRISPR started getting lymphoma.
“You don’t want that,” said David Edgell, who runs a biochemistry lab at Western University in London, Ont. Before you start tweaking the genome of a living person, you want to be assured the gene editing technology is precise, accurate and not toxic, he said.
Researchers and the public are reasonably concerned about CRISPR being so powerful that it potentially gets put to dangerous uses.
“And you can’t do that right now with CRISPR, there’s not enough certainty in the technology to say that,” he said. “In a nutshell, that encapsulates what a lot of people are worried about.”
He compares it to GPS, global positioning technology, in that you can program in a location, “but sometimes you punch in slightly wrong coordinates and the CRISPR will go somewhere else instead of exactly where you want it to go. Those are called off-target effects. If you’re manipulating cell lines in a laboratory, off-target effects aren’t so much of an issue. But for any therapeutic use, or if you want to manipulate the genome in a precise way with only one change, then accuracy and precision becomes a big issue. And just because of the biochemical nature of how CRISPR works, it’s a little more prone to these off-target effects than other types of biochemical reagents that have been used in the past.”
Now, three new research papers, from the University of Toronto, University of California San Francisco, and Edgell’s team at Western, show progress in controlling CRISPR, either by tricking it as Edgell’s work does, or shutting it down completely via a sort of master off switch, as the other two do. In the Toronto work, for example, “anti-CRISPR” proteins were isolated from viruses that infect bacteria and put to work as a sort of “safety valve.”
The idea is not so much to shut CRISPR down in a runaway emergency, but rather to control its activity over time, letting it do its intended work for a brief while, but shutting it down before it has a chance to stray off-target.
“Making CRISPR controllable allows you to have more layers of control on the system and to turn it on or off under certain conditions, such as where it works within a cell or at what point in time,” said Alan Davidson, a biologist at the University of Toronto, in a press release. “We didn’t set out to find anti-CRISPRs, we were just trying to understand how phages incorporate themselves into bacterial genomes and stumbled onto something that I think will be important for biotechnology.”
“Researchers and the public are reasonably concerned about CRISPR being so powerful that it potentially gets put to dangerous uses,” said Joseph Bondy-Denomy, who led the California work. “These inhibitors provide a mechanism to block nefarious or out-of-control CRISPR applications, making it safer to explore all the ways this technology can be used to help people.”
• Email: jbrean@nationalpost.com | Twitter: JosephBrean
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