The scientists have come up with a new innovative device to unveil new drug targets for cancer and regenerative drugs. How will it help?
FREMONT, CA: The team of Shana Kelly, a University Professor in the Leslie Dan Faculty of Pharmacy at the University of Toronto, has developed a portable, chip-like gadget that uses small magnets for sorting significant populations of mixed cell types. The device is thought of being coupled with a CRISPR-based gene-editing technology. The combination of two methods can help scientists to speed up combing via the human genome for potential medicine targets.
Microfluidic cell sorting (MICS) will enable scientists to scour the human genome quicker when looking for genes, and their protein products, which can be targeted by medicines.
In one hour, MICS is able to collect rare cells, in which CRISPR unveiled promising drug targets, from a big, and mixed cell population. A similar experiment will take 20-30 hours if conducted using the gold standard technique of fluorescence-based sorting.
The scientists make use of CRISPR to switch off cells of about 20,000 human genes and notice its effect on the levels of a disease-associated protein, which, for example, helps in the spreading of cancer. This can help in disclosing the other gene candidates along with the proteins they encode, that operate in a similar pathway. These gene candidates can be targeted with medicines for removing the target protein and putting a stop to the cancer spread. The caveat is that genetic screens which lead to mixed cell populations, with a positive effect existing in a vanishingly tiny proportion of cells that have to be gouged out for further research. Many cell-sorting instruments make use of laser beams for separating fluorescently labeled cells, but it requires time.
MICS operates faster due to small magnets that are engineered to bind to the target protein, which leaves the cells behind sprinkled with magnetic particles. The size of MICS is equal to half of a credit card, and its surface is streaked with strips made up of magnetic material that pass the cells from one end of the gadget to another. Once reaching the far end, the cells fall into various collection channels according to the number of particles they carry as a proxy for the quantity of the target protein.
The scientists focused on cancer immunotherapy to test if MICS can unveil new medicine targets. In the test, the immune system was engineered to eradicate tumor cells. They searched for a way to decrease the CD47 protein levels, which shoots a 'don't eat me' signal to the immune system and is usually hijacked by cancer cells as a way of avoiding immune detection. Others have noticed that blocking CD47 directly can result in harmful side effects, which have prompted the Medicine by the Design team to search for the genes which can regulate CD47 protein levels.
Further, a genome-wide CRISPR screen disclosed a gene called QPCTL, which codes for an enzyme that aids camouflage CD47 from the immune system, and that could also be blocked with an off-the-shelf medicine.
The modulation of CD47 levels by acting on QPSTL can trick the immune system in eliminating cancer.
On a regenerative medicine front, MICS will assist in revealing the genes that activate stem cells to transform into specialized cell types. This will help the scientists in coming up with desired cell types for therapy and help them in mitigating cancer cells. MICS has already started attracting considerable interest from the research community as well as industry.