Study shows that gene editing tool CRISPR/Cas9 causes hundreds of unexpected mutations, but researchers remain optimistic.
The discovery of CRISPR in the defence mechanism of bacterial prokaryotic DNA a few years back was a major breakthrough that sent momentous waves through the scientific world. Forming the basis of the gene editing technology CRISPR/Cas9, the new tool allows scientists for the first time to create changes in the genes of living organisms with pinpoint accuracy.
Gene therapies based on CRISPR/Cas9 have already been used to successfully treat diseases where other treatments have failed.
In 2015, gene-modified immune cells from another person was injected into a one-year old girl, Layla, to treat her leukaemia, who then made a remarkable recovery just a few months later.
In 2017, scientists successfully eradicated AIDs from mice by using CRISPR/Cas9 to literally cut out the HIV virus RNA from infected cells in the mice.
Gene editing has been used to increase cell resistance to cytotoxic oxysterol, 7-Ketocholesterol (7KC), which is the cause of a number of age-related diseases including atherosclerosis and Alzheimer’s disease.
However, a study published by Nature Reports showed that CRISPR/Cas9 had the potential to induce hundreds of unintended mutations, which raises some concerns. And although CRISPR/Cas9 was successful in its original purpose (that is, correcting a gene that causes blindness), it also left about 1,500 minor changes and about 100 major changes to the genome.
These changes, also called single nucleotide polymorphisms (SNP), are single nucleotide (A, T, C or G) changes to DNA. While the changes may seem small, a single nucleotide change is enough to alter the protein that a gene produces, or even cause it to stop working. This in turn could cause unexpected diseases to develop in otherwise healthy individuals, raising important ethical questions on how CRISPR/Cas9 research and application should proceed.
Optimism still high.
However, this has not dampened the optimism that researchers have for CRISPR/Cas9. In a statement by Vinit Mahajan, a researcher at the department of ophthalmology at Stanford University and a member of the study, said that all treatments have their side effects – we just have to be aware of what they are.
Jennifer Doudna, a molecular biologist at the University of California, Berkeley, and co-discoverer of CRISPR/Cas9, says that the unintended mutations could’ve been the result of how the tests were conducted in the study, which was different from how it’s done in the majority of laboratories. Earlier research has shown that CRISPR/Cas9 did not affect changes in the genome that were seen as susceptible to accidental mutations. She also stated that the statistical analysis of the Nature report does not hold up to close scrutiny.
So, despite the concerns raised by the Nature study, the first human clinical trials to study CRISPR/Cas9 are now underway. In October 2016, researchers at Sichuan University were the first to inject genetically modified cells into 10 lung cancer patients. Led by oncologist Lu You, the research team took immune cells from the recipient’s blood and used CRISPR/Cas9 to turn off the gene PD-1, that was producing a protein that shuts down the cell’s immune response.
As Daisy Robinton, a scientist at Harvard, told an audience in her talk title “The End of Ageing” at Tedx LondonSalon, “With the discovery of CRISPR/Cas9, we realized that we had this natural way of finding any particular sequence – and targeting it. It could be any strand of DNA or even in the whole genome.”
“Researchers studying that Cas9 protein recognized its function as a gene editing technology and realized that we now had the capacity to use it, as researchers, to snip or delete little bits of DNA with incredible precision. The development of CRISPR/Cas9 as a gene editing technology allows us opportunities to do things that just haven’t been possible in the past.”