Human embryos genetically modified again – this time for HIV resistance

They were trying to genetically modify embryos to be resistant to HIV.

It’s barely been a year since the debate about the ethics of genetically modifying human embryos had started. In a publication in April last year, it was reported that a team of Chinese researchers edited human embryos in an attempt to remove genes responsible for a dangerous blood disorder – ß-thalassemia. Now, another group of scientists in China have successfully carried out the procedure for the second time in history. On this occasion, the team attempted to create HIV-resistant embryos. Both these teams used the CRISPR/Cas9 gene-editing tool.

In this new study, scientists from Guangzhou Medical University tried to add a mutation to embryos instead, attempting to make them HIV-resistant. Similar to the previous report, the experiments were only partially successful, and were carried out using non-viable human embryos that were incapable of growing into adults. This is only the second reported experiment of its kind; published last week in the Journal of Assisted Reproduction and Genetics.

crispr 2

This is the second instance of human embryos being genetically altered using CRISPR/Cas9 (http://bit.ly/25W50rh)

Yong Fan and his team collected 213 fertilized human eggs from 87 patients in a fertility clinic. These eggs contained an extra set of chromosomes eggs making them unsuitable for in vitro fertilization and thus donated for research purposes. Using the gene-editing tool CRISPR, the scientists were able to introduce a naturally-occurring genetic mutation into the embryos. This mutation modifies a gene in the T cells called CCR5. As a consequence of this mutation, the virus cannot enter the T cells and infect it any longer.

The researchers were only able to successfully modify four of the 26 embryos targeted, and some of these embryos also acquired unplanned mutations — a side effect that was similarly observed in the research published last year. After the experiments, the embryos were all destroyed within three days’ time. “It just emphasizes that there are still a lot of technical difficulties to doing precision editing in human embryo cells,” says Xiao-Jiang Li, a neuroscientist at Emory University in Atlanta, Georgia.

“The results are both comforting and disturbing,” said Dr. Peter Donovan, a professor of biological chemistry and development cell biology at the University of California. “The good news is that the technique worked for this group in the same way that it did for the first group. This indicates the reproducibility of the science […] However, this group of researchers also reproduced another finding described by the first group, namely that this type of gene editing also causes off-target effects.”

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CRISPR systems are found in many different bacterial species, and have evolved to protect host cells against infection by viruses (http://bit.ly/1NlQ622)

These inconsistencies, however, have concerned some scientists across the world. The previous report fuelled global deliberations over the ethics of modifying embryos and human reproductive cells. The current study might only serve to exaggerate those.  Some pioneers in the field have called for a moratorium on even such proof-of-principle research. Stem cell biologist Paul Knoepfler pointed out that the group succeeded in editing the gene 5 percent to 15 percent of the time, but created unwanted mutations in the gene—called indels—much more often. “The paper does not in my opinion strengthen the case that CRISPR’ing of human embryos with reproductive intent is ever something that could work well enough to be done clinically,” Knoepfler wrote.

However, there are others who believe that there is still much productive work that can be done, as long as researchers do not cross the clear line of implanting viable genetically-modified embryos into a woman’s uterus. Tetsuya Ishii, a bioethicist at Hokkaido University in Sapporo, Japan, sees no problem with how the experiments were conducted—a local ethics committee approved them, and the egg donors gave their informed consent—but he just questions their necessity.

 At last year’s International Summit on Human Gene Editing, a consensus was arrived at by scientists from the US, UK, and China where they agreed that using viable human embryos in research should not be banned, but that altering the DNA of embryos for clinical purposes was unacceptable.

Human gene editing is currently allowed in the UK under very strict regulations; so far, it’s not legal in the US.

“Studies in mice and non-human primates will undoubtedly be informative but ultimately it will be studies like the ones just published using donated human embryos that will give us the most understanding,” said Donovan, adding: “There is still much to be learned about gene editing in human embryos before it is ready for prime time.”

 

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