Gene-editing breakthrough could spell end of hereditary disease

Gene-editing breakthrough could spell end of hereditary disease

Shoukhrat Mitalipov and his colleagues from Oregon Health and Science University have successfully used the CRISPR Cas9 gene editing technology to wipe out a genetically inherited heart mutation in embryos.

The authors believe their success at avoiding mosaicism also lies in editing early embryos. 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.

The scientists said the procedure was surprisingly effective and that clinical trials could eventually be considered. The work is not likely to spread to fertility clinics either, he said.

Currently, the most reliable way of screening for such inherited defects is by using IVF, screening the resulting embryos for the mutation and transferring only those without the mutation for pregnancy. The technology, which selectively "snips" and trims areas of the genome and replaces it with strands of desired DNA, has previously been used on adult humans and other species. Though it's still in the testing phase, CRISPR has been likened to eugenics or playing God by allowing scientists to create "designer babies" or wipe out diseases through the kind of genetic engineering now limited to plants and lower animals. But so-called "germline" changes - altering sperm, eggs or embryos - are controversial because they would be permanent, passed down to future generations.

"Every generation on would carry this fix because we've removed the disease-causing gene variant from that family's lineage", Dr Shoukhrat Mitalipov, a key member of the team, said.

Researchers in other countries have edited human embryos to learn more about early human development or to answer other basic research questions (SN: 4/15/17, p. 16).

Researchers used CRISPR to prevent an embryo from inheriting a fatal heart condition. "Such technology would ensure that those families afflicted with such diseases no longer need worry about passing it down the family line".

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Other experts said the research was remarkable and had taken gene-editing from "future fantasy to the world of possibility". That would stop them from being vulnerable to hypertrophic cardiomyopathy - and would save their children, too. That research is aimed at understanding basic reproductive and developmental biology, as well as unpicking some of the causes of early miscarriages. "I've never known healthy".

Lanner is also editing genes in human embryos, as a way of learning more about developmental biology. The resulting embryos contain now repaired, mutation-free copies of this gene. Doctors can therefore test and transfer only unaffected embryos. For women ages 35 to 40, pre-implantation diagnosis was used in about one out of four IVF attempts in the USA last year, according to the Society for Assisted Reproductive Technology. But the scientists say that doesn't necessarily mean CRISPR will be as successful once scientists try to remove other diseases.

Newly fertilized eggs before gene editing (left) and embryos after gene editing and a few rounds of cell division (right). The scientists' intervention raised that rate to 72 percent. This technique would only work in the second case.

"CRISPR is just targeting and doing the cutting". Typically, researchers wishing to edit a genome will insert DNA encoding CRISPR components into cells, and then rely on the cells' machinery to generate the necessary proteins and RNA.

There are 10,000 hereditary illnesses caused by a single gene error, including the cancer-causing "Jolie gene" BRCA1 that multiplies a person's chance of breast and ovarian tumours.

But this prospect is still distant: "additional research, as well as an ethical debate will be needed before clinical trials", has taken care to specify the professor Amato. "It's unclear at this point when we would be able to move on", Mitalipov says. But it suggests that scientists might alter DNA in a way that protects not just one baby from a disease that runs in the family, but his or her offspring as well.

Essentially, CRISPR turned the defective paternal version of a gene into a working maternal one. The higher targeting efficiency "suggests that human embryos employ different DNA fix mechanisms than do somatic or pluripotent cells, probably reflecting evolutionary requirements for stringent control over genome fidelity in the germline", the authors wrote in the paper. She said that while pre-implantation genetic screening of embryos is now available, it isn't flawless.