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Silkworms now have a bacterial superpower thanks to CRISPR

The CRISPR immune system from bacteria has been engineered into silkworms, allowing them to fight off a virus that plagues the silk industry
Silkworms are plagued by a lethal virus
Silkworms are plagued by a lethal virus
VCG / VCG via Getty Images

A team in China has made genetically engineered silkworms that can fight off a lethal virus. They did it by giving the silkworms CRISPR: an immune system found in many bacteria. The same approach might protect a wide range of animals and plants from viral diseases.

The silk industry suffers huge losses because of a disease caused by the Bombyx mori nucleopolyhedrovirus (BmNPV). “It would be incredibly important to have virus-resistant silkworm,” says of the University of Oxford, UK, who studies insect silks and their uses.

The key could be CRISPR. It has become famous as the genome-editing tool revolutionising biology, but it evolved in bacteria as a kind of immune system to protect against viruses.

In these bacteria, CRISPR proteins first recognise the DNA of invading viruses, using “guide RNAs” that contain a matching sequence. They then cut up the viral DNA, preventing the virus making more copies of itself.

Healthy genetic modification

of the State Key Laboratory of Silkworm Genome Biology at Southwest University in Chongqing, China, and his colleagues have given silkworms the genes for the CRISPR Cas9 protein, along with guide RNAs targeting BmNPV sequences. They then exposed silkworms to the virus to test their resistance.

The modified silkworms only succumbed when given a dose 1000 times greater than that which killed ordinary silkworms. That’s a far higher level of protection than any of the other teams trying to create virus-resistant silkworms have achieved.

Geneticists have long worked to create disease-resistant plants and animals, with some successes. For instance, in 1998 from complete obliteration by the introduction of a GM papaya resistant to the ringspot virus.

But what protects one organism against one virus seldom works for other organisms and other viruses, so creating virus-resistant plants and animals can take years of trial and error. By contrast, the CRISPR immune system should work in just about any plant or animal. Only the guide RNAs need to change, and that’s easy.

And while CRISPR won’t fight infectious bacteria or fungi, it should work against a wide range of viruses. The Cas9 protein that Dong used only cuts up DNA, so it wouldn’t work against viruses that inject RNA into cells rather than DNA. But in February, a team in Saudi Arabia reported that they had managed to protect tobacco plants from RNA viruses using a that does cut up RNAs ().

GM silkworms

The potential downside of Dong’s approach is that it requires the CRISPR protein and guide RNAs to be continuously produced in every cell. If the CRISPR protein targets silkworm DNA by mistake, it could greatly increase the mutation rate in the silkworm’s cells and make the animal ill. Doctors developing treatments for human diseases are trying to avoid this by ensuring the CRISPR protein will only be present in cells for a few days.

However, the good news is that many teams are reporting that off-target effects are undetectable when guide RNAs are carefully designed. Dong’s team found none in the silkworms.

of the University of California, Berkeley, whose 2012 work helped spark the CRISPR revolution, points out that other researchers have created strains of mice whose cells permanently express Cas9. “The mice seem fine,” she says.

Making silkworms disease-resistant is just one of the aims of genetic engineers. Other groups around the world are modifying silkworms to produce silk that or . The latter makes sense when you consider that spider silk is famed for its strength, but it’s hard to farm spiders.

Frontiers in Microbiology

Topics: Biology / Disease / Diseases / Genetic modification / Genetics / Immune system / Insects