Gene-edited twins in China still face risk of HIV infection
  • Sunday, January 20, 2019
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Gene-edited twins in China still face risk of HIV infection

  • A Chinese researcher claims that he helped make the world's first gene-edited babies. But not everyone supports this controversial experiment.
  • ASSOCIATED PRESS

    He Jiankui, left, and Zhou Xiaoqin work a computer at a laboratory in Shenzhen in southern China’s Guangdong province. Chinese scientist He claims he helped make world’s first genetically edited babies: twin girls whose DNA he said he altered.

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Twin girls whose DNA was altered as part of a controversial effort in China to make them resistant to HIV infection could still contract the virus that causes AIDS.

Certain relatively uncommon strains of HIV would be able to enter their cells if the girls were to come in contact with contaminated tissues or fluids, said Robin Shattock, chairman of mucosal infection and immunity at the U.K.’s Imperial College London.

He Jiankui, the researcher who used a technique called Crispr to manipulate the twins’ DNA when they were in the embryonic stage of development, is facing criticism for exposing the girls to potential lifetime risks that scientists are just beginning to understand. Other widely used prevention approaches would be more reliable and less risky than using the unproven technique to alter their genomes, Shattock said.

“This is a totally ludicrous and unnecessary approach” to infection prevention, he said in a telephone interview. “That’s the dodgy ethical aspect.”

Crispr allows scientists to remove or replace specific genes in living organisms. While it holds promise for addressing a number of DNA-related diseases, scientists are investigating whether it affects people’s chances of cancer or other disorders. Many governments have restricted or banned its use in human embryos because the altered traits can be passed on to future generations with unknown consequences.

YouTube Video

He, based at the Southern University of Science and Technology in Shenzhen, China, announced his work in a YouTube video and is scheduled to release his data Wednesday at a conference in Hong Kong. The university said in a statement that it’s “shocked” at He’s actions, China’s National Health Commission asked for an investigation, and a group of 122 Chinese scientists issued a joint statement decrying the work as “madness.”

“I understand my work will be controversial, but I believe families need this technology, and I’m willing to take the criticism for them,” the researcher said in the video.

Almost 37 million people worldwide have HIV, according to the World Health Organization, though China’s infection rate is among the lowest. He, who was trained in the U.S., said the girls’ father was infected, and he wanted to protect them from HIV.

Transmission from parent to child can be blocked with appropriate use of antiviral drugs, Shattock said. A regimen called PrEP can also keep people at high risk of contagion from becoming infected via other routes.

Daily antiviral treatment presents its own risks, He said in a separate video. HIV remains incurable and kills about 1 million people a year, he said.

Gene editing, “while not applicable to the general public, may be valuable to help a few affected and very high-risk families protect their children from the same fate,” he said in the video.

Alternate Gateway

Working with a small team, He altered a gene that makes a protein called the CCR5 receptor. HIV uses the protein to enter cells that it kills or uses as a hiding place from patients’ immune systems. People with a mutated CCR5 receptor are known to be far less likely to become infected than those with a normal version.

However, HIV has an alternative way of getting into cells, via another receptor called CXCR4, Shattock said. While this version is rarer than those that use CCR5, CXCR4-dependent strains may be involved in as much as 5 percent of infections in some parts of the world, he said. A study of 148 infected women in Botswana in 2012 found that 15 percent had both varieties of HIV, while the rest carried only CCR5-dependent virus.

“It’s very unlikely but it can’t be excluded” that someone would become infected via a strain using CXCR4 to enter cells, he said.

Genes come in pairs — one from each parent. In one of the twins, just one of the two copies was successfully changed, He told the Associated Press. That could mean that child isn’t protected from HIV infection, said Ewan Birney, director of the European Bioinformatics Institute.

Scientists have long focused on using CCR5’s function as cellular gatekeeper to slow the deadly virus. Certain drugs, such as Pfizer Inc.’s Selzentry, cover up the receptor, blocking HIV’s access. The drug’s effectiveness can be blunted when HIV mutates to use the alternate CXCR4 receptor.

Zinc Fingers

Companies have looked at various means of altering CCR5. Sangamo Therapeutics Inc. has used another gene-editing technique, called zinc fingers, to manipulate the gene in patients. While the treatment showed promise, very few have been able to discontinue their HIV drug regimens, Chief Executive Officer Alexander Macrae said Nov. 15 in a presentation in London.

Questions remain about the overall health impact of having a mutated CCR5 receptor. A small study published in 2017 associated the mutation with a heightened risk of death from the flu. Many people have the same deletion in the CCR5 gene that He replicated in his experiment without any apparent ill effects, Birney said.

“But I don’t believe anybody really knows,” what the impact will be, he said in a telephone interview. “And perhaps most importantly, there are really effective ways of ensuring that HIV transmission doesn’t happen with modern drugs.”

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