A team of researchers from the University of Toronto has combined CRISPR-based gene-editing technology with small biomagnetic devices to sort large populations of mixed cell types.
A team of researchers from the University of Toronto has combined CRISPR-based gene-editing technology with small biomagnetic devices to sort large populations of mixed cell types. The combination exponentially speeds up the sorting process to find promising drug targets.
Shana Kelley, a University Professor in the Leslie Dan Faculty of Pharmacy at the University of Toronto said the project, which began as a conversation between colleagues, is now an “engine for the discovery of new therapeutic targets in cells” that is part of her Medicine by Design team project. Kelley’s lab was using portable, magnetic chip-like devices. Those devices were paired with a CRISPR program developed by her colleague, Jason Moffatt, a professor in the Donnelly Centre for Cellular and Biomolecular Research. The two scientists, according to the University of Toronto, reasoned their methods could be combined in order to speed up searches through the human genome for potential drug targets. And, according to Kelley, that reasoning turned out to be spot on. She said the researchers found the combination “worked incredibly well.”
Results of the joint effort, now called MICS, for microfluidic cell sorting, were published in the journal Nature Biomedical Engineering. MICS, the university said, will enable researchers to search the human genome faster when looking for genes and their protein products, which can be targeted by drugs. According to the results, within one hour, MICS can collect rare cells that can be targeted by CRISPR. Using the current standard of fluorescence-based sorting, the same process takes between 20 and 30 hours, the university noted. Kelley’s magnetic cell sorting was initially developed to isolate tumor cells from the blood, but the team now believes repurposing the technology to benefit drug discovery will have a wider impact. MICS is already attracting interest from the pharmaceutical industry and research community, the university said.
As the University of Toronto explained, MICS works faster due to the use of the tiny magnets, which have been engineered to bind to target protein. That binding leaves the cells “sprinkled” with magnetic particles. That allows the cells to be funneled into collection channels based on how many particles they carry as a proxy for the amount of the target protein.
“As many as one billion cells can travel down this highway of magnetic guides at once and we can process that in one hour,” Kelley said in a statement. “It’s a huge gamechanger for CRISPR screens.”
As part of the research, the team focused on cancer immunotherapies, with a particular look at a way to reduce the levels of the CD47 protein. Because some research has shown blocking CD47 directly has harmful side effects, the Medicine by Design team began to look for genes that regulate CD47 protein levels. Using a genome-wide CRISPR screen, the team found a gene called QPCTL “codes for an enzyme that helps camouflage CD47 from the immune system.” That gene can be blocked with an off-the-shelf drug, the team said.
Moffat noted that modulating CD47 levels by acting on QPCTL has potential to “trick” the immune system to target the cancerous cells. While the research is still early, Kelley and Moffat are hopeful about QPCTL’s therapeutic potential. As a result of their early findings, the duo is launching a multi-lab collaboration PEGASUS project, for Phenotypic Genomic Screening at Scale, which will scale up the technology to interrogate a broad range of therapeutic targets.
MICS is also expected to have an impact on regenerative medicine. The technology will help reveal genes that “activate stem cells to turn into specialized cell types, which will make easier harvesting of desired cell types for therapy,” the researchers said.
