New technologies such as the CRISPR-Cas9 offer the possibility of altering an individual’s genome, or even a generation’s genome.

Jennifer Doudna, PhD, a geneticist and professor at the University of California Berkeley and the Howard Hughes Medical Institute, created CRISPR in collaboration with Emmanuelle Charpentier, PhD, of Umea University in Sweden, in 2012.

Out of fear the technology could be misused, Doudna advocated a worldwide moratorium on gene editing that involved heritable changes.

Thus far, no researchers have publicly stated that they have made germline alterations in a human embryo with the intent of nurturing it to birth. But over the past year they have inched closer.

In August, researchers at Oregon Health & Science University in Portland, Oregon, led by biologist Shoukhrat Mitalipov, PhD, for the first time in the U.S. demonstrated the potential to edit human embryo DNA to prevent a congenital heart condition known as hypertrophic cardiomyopathy, which may cause heart failure or sudden death.

Then in October, the New Scientist reported that the CRISPR method was showing promise across a range of diseases in animal studies, including in muscular dystrophy and liver disease.

While this process is “relatively easy” for immune cells or blood stem cells, “this isn’t possible with most bodily tissues,” noted the New Scientist’s Michael LePage.

Matthew Porteus, MD, PhD, associate professor of pediatrics at Stanford University and an NAM committee member, told a Senate, Health Education, Labor and Pensions Committee in November that the best approach for other conditions such as congenital blindness and muscular dystrophy likely involves in vivo gene editing.

Regarding other conditions studied through ex vivo experiments, Porteus said his lab developed a method for correcting mutations of sickle cells in patients’ stem cells. If a cure is found, it might take only a few “tweaks” to then find a cure for other illnesses, such as severe combined immunodeficiency, he noted.

He anticipates seeing multiple CRISPR-Cas9 clinical trials in the U.S. or Europe in the next 12-18 months, Porteus added.

What’s Next for Gene Editing?

Asked about the most notable breakthroughs in the field right now, R. Alta Charo, JD, co-chair of the Committee on Human Gene Editing and a professor at the University of Wisconsin in Madison, spoke of “the developing capacity to do epigenetic editing,” speaking on her own behalf, in an email to MedPage Today.

“[I]t offers the prospect of making beneficial changes that, because they are reversible, in many cases will pose fewer risks,” she said.

As another benefit, this form of gene editing could be used to respond to conditions that stem from a “constellation of genetic factors” rather than a single mutation, reported Wired.

Researchers have already begun testing epigenetic editing in mice for diseases such as diabetes, acute kidney disease, and muscular dystrophy, Wired noted.

“Successful somatic gene therapy” and the OHSU study “pending confirmation by the scientific community” are the most notable breakthroughs of the year, said Jeffrey Kahn, PhD, MPH, director of the Johns Hopkins Berman Institute of Bioethics in Baltimore, and a member of the NAM committee, in an email to MedPage Today.

However, he noted that pre-implantation genetic diagnosis could have replaced gene editing in the OHSU study. In other words, the researchers ignored one of the NAM committee’s key criteria for heritable gene editing: lack of a reasonable alternative.

Others disagreed.

Because the study did not involve a pregnancy or birth “it constitutes purely laboratory research” and would be “permissible” under committee guidelines, said Charo.

“An emerging area in gene editing is harnessing these new precision engineering tools to edit regions of the genome outside of genes,” said Neville Sanjana, PhD, a core faculty member at the New York Genome Center and a professor at New York University, in an email, responding to the same question.

The ‘Dark Genome’ Emerges as Target

Gene editing tools can help to translate these regulatory and noncoding variants, those outside of the genes — less than 2% are actually in the genes themselves.

This area is sometimes referred to as the “dark genome.”

“Most of our genome is actually this ‘noncoding’ DNA and not in genes (less than 2% is in genes). We understand very little about how this noncoding DNA works and how changes in the sequence (primary sequence — not epigenome) results in changes in gene expression and disease,” said Sanjana.

Sanjana also highlighted the approval of “a multitude” of new gene therapies by the FDA for conditions such as congenital blindness, spinal muscular atrophy and different hemophilias, which he said has also generated a lot of excitement.

Although some gene therapies have been around since the 1990s, not all involve gene editing. However, the approvals represent progress, he noted.

“It is clear that this new modality of therapy — adding back a missing or damaged gene — will open new avenues of medicine,” said Sanjana.

“[I]t is a matter of time before gene editing tools are also part of the gene therapy arsenal to aid in curing disease for which we currently have no therapies,” he added.

As always, oversight will remain important to this process.

“The challenge is to find the ‘just right’ regulatory approach for what are new, emerging, and controversial biotechnologies such as gene editing tools. That often requires some tweaking to get right, and I hope that there is willingness to engage in the discussion necessary to find the appropriate balance of control with a path for innovation,” wrote Kahn.