Scientists are getting one step closer to snipping inherited genetic diseases out of human offspring using a gene-editing technique called CRISPR.

For the first time, scientists said, they corrected a gene mutation linked to inherited heart conditions in human embryos using the approach. A study demonstrating the technique was published in the journal Nature on Wednesday (PDF).

Last week, the MIT Technology Review released the first news of this scientific feat, describing the research as the first-known attempt at creating genetically modified human embryos in the United States.

However, Juan Carlos Izpisua Belmonte, a co-author of the study, described it as the first in the world to demonstrate gene-editing to be safe, accurate and efficient in correcting a pathogenic gene mutation in human embryos. Previous attempts by Chinese researchers were unsuccessful at achieving this without safety concerns.

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“This is the first that has been demonstrated as safe and working,” said Belmonte, a professor at the Salk Institute for Biological Studies’ gene expression laboratory in La Jolla, California.

“All cells of the embryo were corrected,” he said. “It seems to be working from these samples that we have chosen, but we need to do much more basic research with many other genes.”

FAQ: Gene editing


While scientists have long been able to find defective genes, fixing them has been so cumbersome that it’s slowed development of genetic therapies. There are several gene editing methods, but a tool called CRISPR-Cas9 has sparked a boom in research as laboratories worldwide adopted it over the past five years because it’s faster, cheaper, simple to use with minimal training and allows manipulation of multiple genes at the same time.


Pieces of RNA are engineered to be a guide that homes in on the targeted stretch of genetic material. The Cas9 is an enzyme that acts like molecular scissors to snip that spot. That allows scientists to delete, repair, or replace a particular gene.


The fresh attention comes from research involving human embryos. In laboratory experiments, a team lead by Oregon researchers used CRISPR to successfully repair a heart-damaging gene in human embryos, marking a step toward one day being able to prevent inherited diseases from being passed on to the next generation. But there’s wide agreement that more research is needed before ever testing the technique in pregnancy.

The biggest everyday use of CRISPR so far is to engineer animals with human-like disorders for basic research, such as learning how genes cause disease or influence development and what therapies might help.

But promising research, in labs and animals so far, also suggests gene editing might lead to treatments for such diseases as sickle cell, cancer, maybe Huntington’s — by altering cells and returning them to the body. Another project aims to one day grow transplantable human organs inside pigs.


Safety is a key question because gene editing isn’t always precise enough; there’s the possibility of accidentally cutting DNA that’s similar to the real target. Researchers have improved precision in recent years, but out-of-body treatments like using cells as drugs get around the fear of fixing one problem only to spark another.


Altering genes in sperm, eggs or embryos can spread those changes to future generations, so-called “germline” engineering. But it’s ethically charged because future generations couldn’t consent, any long-term negative effects might not become apparent for years, and there’s concern about babies designed with enhanced traits rather than to prevent disease.

Earlier this year, an ethics report from the prestigious National Academy of Sciences opened the door to lab research to figure out how to make such changes — and said if germline editing ever is allowed, it should be reserved for serious diseases with no good alternatives and performed with rigorous oversight.


Where you live determines if, or what kind of, research can be performed on human embryos. Some countries, especially in Europe, ban germline research. Britain allows basic lab research only.

In the U.S., scientists can perform laboratory embryo research only with private funding, as the Oregon team did, not with federal taxpayer money. Any attempt to study germline editing in pregnant women would require permission from the Food and Drug Administration, which is currently prohibited by Congress from reviewing any such request.


Researchers also are using gene editing to hatch malaria-resistant mosquitoes, grow strains of algae that produce biofuels, improve crop growth, even make mushrooms that don’t brown as quickly.

Source: The Associated Press

The study was a collaboration between the Salk Institute, the Oregon Health & Science University in Portland and Korea’s Institute for Basic Science.

Scientists estimate that more than 10,000 human diseases may result from mutations to a single gene occurring in all cells of the body, according to the World Health Organization.

Cutting and correcting gene mutations

The study used 75 human zygotes in which the father carried a mutation on the MYBPC3 gene, Belmonte said. The eggs used to produce the zygotes did not carry that gene mutation. The researchers noted that they received informed consent from the donors of the eggs, sperm and embryos used in the study.

The goal was to correct a type of inherited heart condition. A mutation called MYBPC3 is associated with inherited heart conditions, including left ventricular noncompaction, familial dilated cardiomyopathy and familial hypertrophic cardiomyopathy, which affects an estimated one in 500 people worldwide.

Hypertrophic cardiomyopathy also is thought to be the most common inherited or genetic heart disease in the US, according to the Centers for Disease Control and Prevention.

In a lab dish, the researchers used CRISPR, a gene-editing technique, to remove the harmful MYBPC3 mutation from the human zygotes. Then, the zygotes’ own DNA-repair mechanism replaced what was cut out with a copy of a MYBPC3 gene from the mother, which did not carry a mutation, Belmonte said.

“A male research subject known to be heterozygous for this gene mutation was recruited for the study, as were several healthy young egg donors,” Dr. Paula Amato, an obstetrician-gynecologist at Oregon Health & Science University, said Tuesday. She was a co-author of the study.

“CRISPR was introduced at the time of sperm injection,” she said. “Then, DNA repair of the embryos was assessed.”

The researchers found that about 72% of zygotes were properly and safely corrected on the MYBPC3 gene, Belmonte said.

This method significantly differed from studies in which scientists used the CRISPR tool to manually replace what was cut out with whatever the scientists desired.

Researchers in China were the first to reveal attempts to modify genes in human embryos using CRISPR. Three separate studies were published in scientific journals describing Chinese experiments on gene editing in human embryos.

“The previous human studies done in China had very small numbers, and one of them used abnormal embryos,” Amato said. “So we think this is the first, largest study from which you could draw some reasonable conclusions.”

Some gene-editing attempts in human embryos have been problematic, resulting in an issue called mosaicism, in which the corrections made in one gene failed to replicate once that cell divided into two cells, those two cells divided into four cells and so on.

“So when the baby is born, all the cells do not have the mutation anymore. … This study, it shows that we can correct the embryo and then, after the division, all the cells are corrected, so there’s not what we call mosaicism,” said Belmonte, who is also a member of the National Academies of Sciences, Engineering and Medicine’s committee on human gene editing.

This year, the academies published a report on human genome editing that addressed potential applications of the technology, including the possible prevention or treatment of inherited diseases or conditions.

The future of gene editing

Though the researchers have expressed enthusiasm around their new study, they also noted that the findings must be replicated in followup research before this gene-editing approach can move forward to clinical trials.

“The fact that it is, apparently, a new and poorly understood mechanism and it is not the now standard CRISPR ‘cut and replace’ method adds to the time needed for research into its safety and effectiveness,” said Hank Greely, professor of law and genetics at Stanford University, who was not involved in the new study.

Yet future research can come with some political challenges, Amato said.

“First of all, there are regulations regarding use of federal funds for embryo research, so the (US National Institutes of Health) does not currently support embryo research, so that’s one barrier. The other barrier is, the (US Food and Drug Administration) is prohibited from considering any clinical trials related to germline genetic modification,” she said.

In this new study the embryos were only allowed to mature to day three after fertilization before they were disaggregated, or isolated into various components, for further analysis.

In the far-off future, a clinical trial could include transplanting corrected embryos into a uterus with the goal of establishing pregnancy and then monitoring the embryos as they develop into children.

Still, “it is way too early to contemplate implanting the edited embryos for the purpose of actually establishing a pregnancy,” said Dana Carroll, a professor of biochemistry at the University of Utah who was not involved in the new study but has used CRISPR in his own research.

“The genome editing tools are currently not sufficiently efficient and specific to be reliable, and regulatory and oversight processes have not been established,” Carroll said, adding that the work on the new study was “well-done” and “well-presented.”

“The authors have made an important discovery regarding the repair of CRISPR-induced DNA breaks in human eggs just at the time of fertilization,” he said.

“This information will help to guide ongoing research, and it demonstrates that research on early-stage human embryos will be necessary to establish safe and effective procedures in the long run,” he said. “There is still a lot of work to do to understand repair processes in very early embryos and to optimize the use of the CRISPR reagents, but this study makes a valuable contribution.”

Some CRISPR critics have argued that gene editing may give way to eugenics and to allowing embryos to be edited with certain features in order to develop so-called designer babies.

However, the researchers wrote in their study that they hope CRISPR could be considered as an alternative option to preimplantation genetic diagnosis, also known as PGD, for couples at risk of passing on an inherited disease.

‘This opens up the possibility for those embryos’

PGD, developed about a quarter-century ago, is a genetic testing procedure typically conducted after in vitro fertilization to diagnose a genetic disease or condition in an embryo before it is implanted.

Since the human genome contains two copies of each gene — paternal and maternal alleles, or variant forms of genes — a mutation affecting only one allele is called heterozygous.

When only one parent carries a heterozygous mutation on a gene, about half of the embryos from that parent should be mutation-free while the others would have the mutation. Selectively, the parents’ doctor would chose the healthy embryos to be implanted and discard the embryos with the mutations, Belmonte said.

Sometimes, “a couple that wants to have a baby and they have a mutation, they may not have enough embryos to choose from,” he said. This is when CRISPR can come in.

“This technology, independent of the embryos that are there, it would go on and correct all of them. … This opens up the possibility for those embryos,” he said. “That’s important because after the first implantation, if it doesn’t work, you can do it again.”

The researchers wrote in their study, “PGD may be a viable option for heterozygous couples at risk of producing affected offspring. In cases when only one parent carries a heterozygous mutation, 50% of embryos should be mutant. In contrast, targeted gene correction can potentially rescue a substantial portion of mutant human embryos, thus increasing the number of embryos available for transfer.”

Using CRISPR in that way remains a long way off.

Shoukhrat Mitalipov, director of the Oregon Health & Science University’s Center for Embryonic Cell and Gene Therapy, helped lead the new study. In 2013, Mitalipov and his colleagues reported the first success in cloning human stem cells, reprogramming human skin cells back to their embryonic state. In 2007, a research team led by Mitalipov announced that they created the first cloned monkey embryo and extracted stem cells from it.

Now, when it comes to using CRISPR to correct gene mutations in embryos, Mitalipov said Tuesday, “We’ve done some ground work. … There is still a long road ahead, and it’s unclear at this point when we will be allowed to move on.”

CNN and The Associated Press contributed to this report.