Excitement and Apprehension Over Genetic Breakthrough
For Professor Ronald Cohn, Chair of the Department of Paediatrics, news of a world-first gene editing discovery that fixed a disease-causing mutation in a human embryo brought with it a mix of scientific excitement and ethical concern.
A team of researchers from the United States, South Korea and China used a genetic engineering tool called CRSIPR to correct a faulty gene that causes hypertrophic cardiomyopathy, a common heart disease that can lead to sudden cardiac arrest, particularly in young people.
“They’ve been able to achieve something other people have tried before unsuccessfully. It’s a huge accomplishment,” says Cohn, who also belongs to the Department of Molecular Genetics and whose lab uses CRISPR technology to research somatic, or non-reproductive, cell therapy. “But I think the steps necessary to move this discovery toward one day having a clinical application are still very far away.”
Scientists at Oregon Health and Science University and their international collaborators used the enzyme CRISPR-Cas9 to cut a specific sequence from mutated genes in donated human eggs. The team also reported that in removing the mutation, the embryos’ future generations would also carry the repair.
Cohn says when it comes to working with the germline — the inherited materials from eggs and sperm that could be passed along to potential offspring — he has significant reservations.
Although the researchers behind the paper didn’t find any side effects, Cohn says more experiments are needed to be certain the process won’t result in unintended consequences to future generations of embryos. As well, more research will need to be done to determine whether edits will have the same effects in maternally inherited and paternally inherited genes, as well as to other cells and mutations.
A test called preimplantation genetic diagnosis (PGD) is already clinically available. It can identify specific inherited disorders including cystic fibrosis, sickle cell anemia and Huntington’s disease within an embryo, allowing prospective parents to choose one without the disease before proceeding with in vitro fertilization.
“The question now becomes, ‘why would you want to go through the risk of editing a genome when PGD is already available?’” says Cohn.
Just last month Cohn, who is also Co-director of the Centre for Genetic Medicine and Chief of Clinical and Metabolic Genetics at the Hospital for Sick Children (SickKids), and his team published its own breakthrough study. In this instance, the team used CRISPR to correct a mutation that causes a form of congenital muscular dystrophy in mice.
In 2015, Cohn’s lab was first to remove a duplicated gene using the gene editing tool. That study involved a cell from a patient with Duchenne muscular dystrophy (DND). The researchers used CRISPR like a pair of scissors to remove the genetic duplication that causes DND and fully restored its function.
Cohn is one of a number of researchers at the Faculty of Medicine using CRISPR. He says the technology has taken the scientific world by storm, enabling important physiological and pathophysiological work to be done both in cell systems and animal models. It has also helped speed up the pace of discovery.
Last year, professors Alan Davidson and Karen Maxwell co-discovered how to turn off CRISPR using three proteins that block the genome editing activity. That finding allows researchers greater precision over the edits being made to a gene, allowing them control over what stage of a cell’s life they may want to use CRISPR.
In addition to using the gene editing tool in her lab, University Professor Janet Rossant in the Departments of Molecular Genetics and Obstetrics and Gynaecology is part of an international committee of scientists and bioethicists that developed criteria that should be met before clinical trials involving DNA editing clinical trials can be allowed to proceed.
Cohn hopes the valuable technology will one day help treat disease in living patients. If — or when — it does, Cohn says CRISPR has the potential to change the world.
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