The breakthrough gene-editing technique known as CRISPR-Cas9 has created a huge buzz in the science world because of its medical promise. For example, scientists might one day be able to prevent genetic diseases by fixing DNA sequences with the precise gene-editing tool – or at least, that’s the hope.
“It’s a game-changing technology, without doubt,” says Dr. Jerry Pelletier, a McGill University Professor in the Department of Biochemistry, who believes that the full potential of the gene-editing technique known as CRISPR-Cas9 remains untapped.
“CRISPR technology is basically based on two things: it’s a protein, and RNA that will get that protein to a DNA address and allow you to do a modification at that address,” Pelletier explains.
One way Pelletier is extending the technology is to try to stimulate specific mRNA (“Messenger RNA”) molecules to make more protein.
In certain diseases, Pelletier says, the mutation of the gene doesn’t completely knock out gene function. Modifying CRISPR to target mRNA instead of DNA may also hold therapeutic potential.
“Sometimes you have mutations that just decrease the activity of the protein. So if you could just get the activity back up to a certain threshold or get the amount of faulty protein above a certain threshold, in principle, you might have beneficial effects.”
That research is just one of the projects Pelletier is involved in that benefit from funding from the Richard and Edith Strauss Foundation.
In his lab in the McIntyre Medical Building, Pelletier’s research program also includes a project aimed at finding new drugs and ways to block Myc, an oncogene that leads to the development of many cancers.
“We’re looking for inhibitors of Myc. If there’s one cancer gene you want to target, it’s Myc. That’s a big one. And to this date, it’s been a very difficult protein to drug, to target,” Pelletier says.
Using CRISPR-Cas9, Pelletier and his research team have engineered cell lines to help identify molecules that will act as a toggle switch, turning a specific gene on or off. “In the context of cancer, obviously we want something that will turn it off,” he says.
“Now you can come in with drugs and see what turns on that gene or turns if off.”
It’s hard to know in real time when you treat a cell with a drug how the gene expression changes, Pelletier explains. Current techniques are labour-intensive and expensive. “But with CRISPR now, you can drop in a gene that creates a fluorescent protein at the DNA address of interest. The presence or absence of fluorescence then indicates whether the drug turns on or off your gene of interest. It’s very simple.”
The ultimate positive outcome from this research would be to identify a specific molecule that blocks Myc, which Pelletier predicts would be a potent anti-cancer drug.
Game-changing research made possible by philanthropy
Pelletier receives significant funding for his research from the Richard and Edith Strauss Foundation, and values its approach. He likes that the Foundation stays in touch with his research team and visits every year.
“In the case of CRISPR, we were able to rapidly mobilize people to work on this. If I had to write a grant and wait a year to start that project. I’d be behind in the game.”
He also appreciates the Foundation’s approach. “If you’re doing good science, they support that.” It doesn’t necessarily have to result in a cure in five years, an expectation that Pelletier calls “totally unreasonable. That’s not where game-changing technology comes from.
“It’s a knowledgeable Foundation. They’re quite aware of what it takes to do research and the amount of time that it takes.”
Pelletier is also involved in immunotherapy research led by Dr. Michel Tremblay, James McGill Professor in the Departments of Biochemistry and Oncology. They’re waiting for approval from Health Canada to go to clinical trial on a new immunotherapy treatment that was developed in Dr. Tremblay’s lab for Chronic Myeloid Leukemia (CML) in collaboration with Dr. Pierre Laneuville, Medical Director of the Cell Therapy Laboratory at the MUHC Research Institute.
Funding from the Strauss Foundation allowed them to complete the pre-clinical work, Tremblay says. The new therapy is aimed at patients who still have tumour cells following treatment and can’t go off medication, with the hope of curing them, and also sparing the government the high cost of the drugs.
The Strauss Foundation was also the catalyst behind the launch of the McGill Stem Cells and Regenerative Medicine Network and provided funding to support it. Before its creation, McGill was heavily involved in stem cell research, but was not recognized for its expertise on the Canadian scene, according to Tremblay.
Stem cell research now spans six faculties at McGill – engineering, law, arts, science, medicine and dentistry – and more than 30 departments.
“The network already has been a remarkable and positive contributor for expanding this field at McGill,” says Tremblay, noting it has fostered interactions and collaborations among different groups at McGill. It hosts an annual symposium and is increasing McGill’s footprint in Canada on stem cells, he says.
It all began with the Strauss Foundation encouraging McGill to organize its efforts in stem cell research, Tremblay says.
“Philanthropy is money, it’s true. But it’s vision,” Tremblay adds. “And a philanthropist that also has a vision of something important, who can listen to the need of the recipient, and understand the dynamic, can make a fantastic difference.”