Apr 12 2016

Study used CRISPR technology to introduce HIV-resistance mutation into embryos

DNA eraser
Researchers from the Guangzhou Medical University in China have reported the use of CRISPR gene editing in human embryos to try to make them resistant to HIV infection. A total of 213 fertilized human eggs were collected from 87 patients of in vitro fertility therapy. The embryos were unsuitable for implantation because they contained an extra set of chromosomes. They were destroyed after the experiment.
CRISPR–Cas9 genome editing was used to introduce into some of the embryos a mutation that cripples an immune-cell gene called CCR5. Some humans naturally carry this mutation (known as CCR5Δ32) and they are resistant to HIV, because the mutation alters the CCR5 protein in a way that prevents the virus from entering the T cells it tries to infect.
Genetic analysis showed that 4 of 26 human embryos targeted were successfully modified. But not all the embryos’ chromosomes harboured the CCR5Δ32 mutation — some contained unmodified CCR5, whereas others had acquired different mutations.
“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. He thinks that researchers should eliminate these problems in non-human primates, for example, before continuing to modify the genomes of human embryos using techniques such as CRISPR.
The paper is the second published experiment of gene editing in humans; the world’s first report on gene editing in humans came in April 2015 from another Chinese team. This fuelled a global debate over the ethics of modifying embryos and human reproductive cells. Among the concerns are the following:
It would be difficult to control exactly how many cells are modified. Increasing the dose of nuclease used would increase the likelihood that the mutated gene will be corrected, but also raise the risk of cuts being made elsewhere in the genome.
In an embryo, a nuclease may not necessarily cut both copies of the target gene, or the cell may start dividing before the corrections are complete, resulting in a genetic mosaic.
The current ability to perform quality controls on only a subset of cells means that the precise effects of genetic modification to an embryo may be impossible to know until after birth.
Because of such concerns, some countries discouraged or prohibited this type of research – in western Europe, 15 of 22 nations prohibit the modification of the germ line.
Key to all discussion and future research is making a clear distinction between genome editing in somatic cells and in germ cells. A voluntary moratorium in the scientific community could be an effective way to discourage human germline modification and raise public awareness of the difference between these two techniques.