Research 4 min read

A Modified CRISPR Tool Creates New Treatments for Diseases

Researchers hope epigenetic editing can treat diseases like type 1 diabetes and muscular dystrophy.

By Kelsey Kennedy featured image Meletios Verras / Getty Images

Instead of making permanent gene modifications with a common DNA editing tool, researchers can now make temporary changes thanks to some clever modifications. Scientists at the Salk Institute described their new technique in a paper published in Cell earlier this month.

The team, led by Juan Carlos Izpisua Belmonte, altered the CRISPR/Cas9 system — a genome editing technology that normally creates double strand breaks in DNA — to simply turn genes off or on without any permanent changes to the genome. “We didn’t disrupt the DNA, we changed the gene function,” says study coauthor Hsin-Kai Liao.

“Sometimes, to cure the disease, we don’t need to really make a correction, we just need to overcome the phenotype and overcome the disease,” he says. By avoiding deleting or adding anything to genes, their technique circumvents concerns of unwanted mutations from rogue CRISPR cuts in the DNA. The new epigenetic CRISPR technology can also be used to treat diseases or slow down symptoms that arise from a constellation of genetic factors rather than being limited to single mutation-based disorders that traditional genome editing tools treat. The team has already demonstrated its effectiveness in three different mouse models of human diseases, and they plan to study more in the future. Liao says the experiments will soon pave the way for human trials.

Here are some of the conditions the team has tackled using the epigenetic editing system, and other CRISPR research to look for in 2018.

Acute Kidney Injury

Sudden damage or loss of kidney function is one type of disease that can be treated with epigenetic modifications. That’s because this type of kidney failure isn’t usually caused by genetic mutations, but by the accumulation of toxic chemicals or other harmful environmental factors, says Liao. Other cases of declining kidney function are simply a result of aging, he says. But in mice with kidney problems, Liao and his colleagues successfully used their epigenetic CRISPR tool to turn on two genes: one that helps protect organs from damage but becomes less active as we age, and another that is responsible for anti-inflammatory effects after kidney injury. Turning these genes on helped the mice live longer with healthier kidneys.

Type 1 Diabetes

Treating type 1 diabetes with the epigenetic CRISPR tool requires a different approach. In their mouse model, the Salk Institute team still turned on a gene, but instead of protecting an organ like the kidney, this gene — known as Pdx1 — triggers a cellular transformation. “It’s like one cell type becomes the other cell type,” says Liao. This gene is vital for pancreatic development, he says, and it can also help some liver cells to change into insulin-producing cells like those in the pancreas. As a result, the treated mice had lower blood glucose levels, and while Liao says the effect wasn’t as strong as they had hoped for, it is a promising start.

Muscular Dystrophy

Both Duchenne and Becker muscular dystrophy are usually caused by mutations in a single gene on the X chromosome, which causes a fatal deficiency of the protein dystrophin in patients’ muscles. But a replacement dystrophin gene is too large to be suitable for traditional CRISPR’s viral delivery system, says Liao. So his team found two ways to work around this problem. They reduced symptoms in some mice by turning on the Klotho gene, which helped the mice build muscle mass. The other method used the modified CRISPR technology to turn on the Utrophin gene, which encodes a protein very similar to the one encoded by dystrophin. The replacement proteins, in turn, helped reduce symptoms in mice.


Liao and his team are also starting to study how their technique can be used to combat aging. “Everybody gets old,” says Liao, and “in the majority of cases, they’re not getting older because they have a gene mutation.” Instead, it’s a result of the reduced expression of genes like Klotho, and damage from a lifetime of exposure to environmental factors, like UV radiation and pollution. By toggling epigenetic changes like switches, the researchers hope to slow the aging process, or at least minimize symptoms of age-related diseases, such as macular degeneration and hearing loss, he says.

Heart Disease, Lung Disease, and Beyond

Liao says researchers from other labs have also expressed interest in using their technique for treating conditions, such as heart disease and lung disease, that are influenced by environmental factors. If scientists can identify genes to turn on or off to compensate for a disease’s symptoms, the tool can be used. Researchers can also use it for basic research, to discern the function of various genes, and to identify more diseases suitable for treatment with the new epigenetic CRISPR in the future, says Liao. “Our approach is not only for therapeutic studies,” he says.