Using his knowledge of how genes are organized and repaired in human cells, Dr. Graham Dellaire, Dalhousie Medical School’s Cameron Research Scientist in Cancer Biology, has developed a technique that could make gene therapy more effective and safer to use. His work was recently published in Nucleic Acids Research and Nature.
CRISPR, named 2015’s breakthrough discovery of the year, stands for “Clustered Regularly-Interspaced Short Palindromic Repeats.” It can accurately target and edit DNA, offering the potential to cure genetic diseases and find new treatments for cancer.
To apply CRISPR in non-dividing cells—such as those in muscle and brain tissue—researchers must first make them behave like cells that divide. They do this by turning on a cellular process called homologous recombination, which protects DNA; the recombination allows a cell’s genes to be manipulated and rearranged without the possibility of causing more harm than good.
In his laboratory at Dalhousie Medical School, Dr. Dellaire came up with a fluorescent tagging technique that allows scientists to identify when gene targeting has been successful in a cell—even in those that don’t divide.
Up to now, CRISPR has been used to treat diseases that affect parts of the body comprised of cells that divide, such as the blood.
This new knowledge will enable gene therapy to be applied to disorders of the musculoskeletal and nervous systems. It could also be used to fight certain types of infections.
Partnering with the Vancouver-based Centre for Drug Research and Development (CDRD), Dr. Dellaire is working on identifying molecules that can be commercialized and developed into drugs. Currently funded by the Canadian Institutes of Health Research, he’s also looking for more research money.
More than 20 years ago, children born with a genetic disorder called severe combined immunodeficiency were the first people to be treated with gene therapy. It led to leukemia.
While CRISPR’s still not efficient enough to be better than using viruses for gene therapy, it’s getting there.
Using his fluorescent screening technique, Dr. Dellaire found that some molecules are capable of enhancing gene targeting by up to six-fold. However, they’re potentially too toxic for use in patients, so there’s a need to find new ones.