Gene editing opens new doors in disease fight

A breakthrough procedure snips mutant DNA from embryos at risk for heart disease
Aug. 7, 2017


Mention the word “editing” and most of us think of inserting commas, moving paragraphs around the page, correcting misspellings and the like in reports or manuscripts. But scientific news released last week placed the word far from the realm of red ink and pink erasers.

In a report published Aug. 2 in the journal Nature,  researchers from Oregon Health and Science University describe a procedure for editing the DNA of human embryos. The specific target: genetic mutations linked to hypertrophic cardiomyopathy (HCM), which causes heart muscle to thicken and increases the risk of heart failure and death.

The procedure used technology called CRISPR-Cas9, which in very simple terms conducts a surgical strike on errors in an individual’s genetic code. The elements of the attack are twofold. One is a piece of RNA that is designed with online tools to bind to DNA near a specific point – the mutation – in the genetic sequence. It’s called “guide RNA.” That’s because it points the second element of the process, the enzyme Cas9, to the mutation. Cas9 cuts the twin strands of the rogue DNA. The cell may then repair itself or a piece of normal, healthy DNA can be inserted.

Get with the program

This is a photo of Matthew Taylor, MD, PhD. Taylor is director of the Adult Genetics Clinic at UCHealth University of Colorado Hospital.
Matthew Taylor, MD, PhD, director of the Adult Genetics Clinic at UCHealth University of Colorado Hospital, says the new gene editing therapy will help to spur further research at institutions like the Center for Personalized Medicine on the University of Colorado Anschutz Medical Campus. The technology, he adds, is “disease agnostic” and applicable to addressing a wide variety of genetic illnesses and conditions.

The idea that scientists might edit genetic errors that cause human misery is not new, noted Matthew Taylor, MD, PhD, director of the Adult Genetics Lab at UCHealth University of Colorado Hospital and associate director of the Center for Personalized Medicine on the University of Colorado Anschutz Medical Campus. The center is home to a DNA biorepository and a budding hub of genetic research aimed at developing targeted therapies for disease.

In the relatively recent past, researchers designed proteins that target specific sequences of the genetic code, Taylor said. But CRISPR-Cas9 makes the job easier because of the precision of guide RNA and the relatively short time that it takes to program it.

“The advantage of CRISPR is that it offers much better specificity for targeting parts of the DNA that we are interested in,” Taylor said. “We can also design experiments in days and weeks, as opposed to months and months. The technology is a game-changer because we can solve problems with targeting DNA much more efficiently.”

Broad application

The significance of the current research lies less in the targeting of HCM specifically than in the proof of the CRISPR-Cas9 editing concept, Taylor said. Genetic tests can already reveal whether embryos from in vitro fertilization have the mutation for HCM. (Embryos from a parent with the HCM mutation have a 50-50 chance of inheriting it.) Those without it are selected for reproduction, thus ensuring that the trait is not passed on to offspring. Gene editing isn’t needed in that instance.

The work of the Oregon researchers, however, validates the broad idea that targeted genetic editing can be done on viable embryos without causing collateral damage.

“That’s a pretty big deal,” Taylor said, “but HCM may not be the disease we wind up focusing on.” He noted that biomedical research often yields breakthroughs that are important in treating specific diseases, but have little effect on others. A discovery in muscle disease, for example, generally has no relevance to, say, diabetes, Taylor said.

The CRISPR/Cas9 approach, by contrast, relies on targeting genetic mutations in general, opening the door to research in many medical areas.

“Once the technology is applicable to one disease, it will be quickly adaptable to many others,” Taylor said. “It’s disease-agnostic.”

In addition, Taylor said, the research could give new hope to people with genetic diseases, such as some forms of deafness or blindness, that for some couples could carry a 100 percent of risk of being passed on to children.

“With these diseases, we don’t have a chance of selecting embryos,” he said. “For these parents who want biological children, this type of approach could also be applicable.”

Gripping a slippery slope

The rapidly expanding world of gene editing continues to raise questions, Taylor acknowledged. For example, the FDA probably will have to decide if each new editing approach will require separate approval, as drugs and other therapies do, or if the agency will approve the general technique for more than a single disease.

The work also raises ethical questions related to what restrictions, if any, should be placed on gene editing. Oregon Health and Science University convened an 11-member Innovative Research and Advisory Panel, which included, among others, clinicians, bioethicists and a lay member. The panel allowed the research that led to the HCM success, but only with significant oversight of “gene correction technologies in human embryos.”

The fears of some that gene editing opens the door to developing “designer babies” or master races “seem far away,” Taylor said. But he added that ethical debates over biomedical technology will continue and probably intensify.

“The writing has been on the wall for a while,” he said. Parents have long been able to get information about the sex of their child and have used it to make reproductive decisions, he noted. “We’re already doing embryo selection for diseases,” he added.

He predicted that the impact of genetic editing, in various forms, will be incremental, as will be the responses to it.

“The technology has opened the doors wide to researchers and the development of new therapies,” he said. “It should be done within the context of biomedical research, with ethical concerns addressed and properly adjudicated.”



About the author

Tyler Smith has been a health care writer, with a focus on hospitals, since 1996. He served as a writer and editor for the Marketing and Communications team at University of Colorado Hospital and UCHealth from 2007 to 2017. More recently, he has reported for and contributed stories to the University of Colorado School of Medicine, the Colorado School of Public Health and the Colorado Bioscience Association.