The public was agog – and a little nervous – when the announcement came out this summer that researchers had “edited” the genes of human embryos, removing a mutation that causes a potentially fatal heart disease.
The embryos were created for the research and will not be implanted. But the study is intended to show that CRISPR/Cas9 technology could be used to remove disease-causing genes effectively and efficiently, not just creating a healthy embryo but allowing the edited genes to be carried into future generations, potentially eliminating the disease from the gene pool.
The number of inherited diseases—or increased risk of disease—that might be avoided this way is staggering. But the concerns are big ones: At what point might this lead to designer babies? Will we reach the point of thinking that genes linked to basic individual traits such as short height or curly hair are problematic? Even if such a thing should never happen, there are worries about making changes to the human germline that will be inherited from that point on. The potential consequences are unknown.
But there’s a less controversial side of gene editing with CRISPR/Cas9 that has life-changing potential for people with many diseases and conditions, including diabetes. Various research projects are under way to find treatments or possibly cures by modifying people’s cells.
CRISPR stands for “clustered regularly interspaced short palindromic repeats,” segments of the genetic code. Cas9 is an enzyme that has been likened to scissors that, with the guidance of CRISPR, can cut DNA with extraordinary precision, removing a segment and replacing it with a new one.
The newest research on using CRISPR/Cas9 to treat diabetes came out in August. Researchers created genetically edited skin grafts that protected mice from diabetes and from gaining larger amounts of weight that are associated with Type 2 diabetes. The idea is that such grafts might be usable in humans one day as long-term replacements for insulin shots.
The researchers “inserted the gene for glucagon-like peptide 1 (GLP1), a hormone that stimulates the pancreas to secrete insulin,” the University of Chicago announced. “This extra insulin removes excessive glucose from the bloodstream, preventing the complications of diabetes. GLP1 can also delay gastric emptying and reduce appetite.”
There’s a history of promising mouse studies that fail to translate into human diabetes treatments, but the researchers don’t see the same problems for this technology because skin grafts have long been used effectively for human burn victims.
“Skin progenitor cells have several unique advantages that are a perfect fit for gene therapy,” the university announcement said. “Human skin is the largest and most accessible organ in the body. It is easy to monitor. Transplanted skin can be quickly removed if necessary. Skins cells rapidly proliferate in culture and can be easily transplanted. The procedure is safe, minimally invasive and inexpensive.”
Other researchers have been working on more expansive treatments for diabetes using CRISPR/Cas9.
Last year, Lund University Diabetes Center in Sweden reported that researchers there, working with rats, had turned off an enzyme that regulates a gene associated with diabetes.
“The results are decreased cell death and increased insulin production in the genetically modified pancreatic beta cells,” the center announced.
The researchers examined a group of enzymes called HATs, or histone acetyltransferases, involved in regulating the TXNIP gene. “The TXNIP gene, in cases of high blood sugar levels, leads to beta cell death and reduced insulin production,” the diabetes center reported.
They found the gene activity of those enzymes was twice as high in diabetic cells than healthy ones. They then used CRISPR/Cas9 to remove and replace a genetic sequence that controls the enzymes.
“This resulted in reduced TXNIP gene activity and thereby reduced cell death and increased insulin production,” the diabetes center announced.
At a more basic-research level, a researcher at the Walter and Eliza Hall Institute in Australia won a grant in 2015 to determine whether CRISPR technology could be used to locate rogue immune cells that attack the pancreas, causing Type 1 diabetes.
And a researcher at the Joslin Diabetes Center in Boston has been using CRISPR-Cas9 to create mouse models of Type 1 diabetes for use in research.
The technology is still in early experimental stages for the most part, and scientists have some concerns about whether its high precision is precise enough.
They’ve noted that the scissoring and replacement might make unanticipated changes to other parts of the genome, called “off-target effects.”
“We think we can get off-target effects to less than 1 percent, but we need to do better,” Dr. J. Keith Joung of Massachusetts General Hospital told Stat News in 2016. The article raises questions about whether scientists are so excited about their new ability to cut out troubled patches of genetic material and replace it, that they’re not paying enough attention to the problems even small imperfections in the technology might cause.
At the same time, such concerns aren’t going to slow the pace of technology that seems to offer so much hope for so many diseases and conditions.